Undergoing Stem Cell Transplantation Research Articles

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT

AbstractSelecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P < .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P < .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P < .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn's disease.

Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure. This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence. The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure. A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% vs 81.6% at 3 year, P = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture (P = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively. Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

Music Listening in Stem Cell Transplantation and Acute Myeloid Leukemia: A Randomized Clinical Trial

ContextMusic listening (ML) has been shown to have a beneficial effect on patients with cancer. However, novel intervention approaches are needed. ObjectivesWe aimed to determine whether ML based on the iso-principle, conducted using a mobile application (GloMus), improves symptom burden, quality of life (QoL), anxiety, and depression in patients undergoing stem cell transplantation (SCT) and intensive induction chemotherapy for acute myeloid leukemia (AML). MethodsIn this randomized controlled clinical trial, we assigned 71 patients to the ML or standard care (SC) groups, stratified by the reason for admission (AML, allogeneic-SCT, or inpatient/outpatient autologous-SCT). Upon admission, participants in the ML groups were invited to undergo daily ML sessions designed to change negative moods into positive ones (iso-principle). The intervention consisted of listening to pre-recorded classical music ordered by beats per minute and tonality. Symptom burden (Edmonton Symptom Assessment System-Revised) was assessed in the ML groups before and after each session. Anxiety, depression (Hospital Anxiety and Depression Scale), and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation/Leukemia) were measured weekly in the ML and SC groups. ResultsSymptom burden in both allogeneic- and inpatient autologous-SCT ML groups reduced after the intervention. In all experimental groups, clinically important improvements were observed after ML sessions. No differences were found between the groups (ML vs. SC) at different weeks of admission regarding anxiety, depression, and QoL. ConclusionsML based on our innovative iso-principle strategy, conducted using GloMus, reduced the symptom burden in patients undergoing allogeneic- and inpatient autologous-SCT (ClinicalTrials.gov number, NCT05696457).

Palonosetron in pediatric patients: A single-center, retrospective evaluation of policy and clinical practice guideline discordance.

Clinical practice guidelines (CPGs) recommending palonosetron for the prevention and management of chemotherapy-induced nausea and vomiting (CINV) were adapted for use at our institution. Palonosetron was restricted for use in patients experiencing breakthrough CINV and receiving highly emetogenic chemotherapy (HEC) or undergoing stem cell transplant conditioning and in patients with refractory CINV receiving HEC. Given the significant cost of palonosetron, we aimed to determine the proportion of chemotherapy blocks where palonosetron use was discordant with the institutional policy or source CPG. A retrospective review of the health records of patients who received palonosetron between 1 July 2019 and 30 June 2020 was undertaken. Details of palonosetron use, antiemetic regimen and the date and time of each vomit during the acute and delayed phases were collected for each chemotherapy block where palonosetron was given. Discordance with the institutional policy and the source CPG was determined by assessing the indication for palonosetron and the dose. In the subset of chemotherapy blocks where information regarding vomiting episodes was available, the extent of acute phase chemotherapy-induced vomiting (CIV) control was reported. Four hundred thirty-eight chemotherapy blocks, representing 122 patients (mean age 9 years), receiving 595 palonosetron doses were included. Palonosetron use was discordant with institutional policy during most (72%; 314/438) of the chemotherapy blocks analyzed. However, palonosetron use was concordant with the source CPG during most chemotherapy blocks (74%; 326/438). Complete CIV control during the acute phase was observed in 66% (195/295) of chemotherapy blocks where palonosetron was given, irrespective of concomitant antiemetics administered. The majority of palonosetron use at our institution was discordant with institutional policy, but concordant with the source CPG. Our institutional policy has since been updated to be more aligned with the source CPG.

Charting a path forward: Promising outcomes of convalescent plasma therapy in the care of severely B-cell depleted patients with persistent COVID-19.

Patients with severe B-cell depletion related to hematological malignancies or B-cell targeted therapy suffer from impaired antibody responses to SARS-CoV-2 and are at risk for prolonged COVID-19. In this population, COVID-19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B-cell depleted patients with persistent COVID-19 treated with CCP. This analysis included all consecutive severely B-cell depleted patients with persistent COVID-19, receiving CCP at Rambam between 01.2022-02.2023. Persistent COVID-19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS-CoV-2 nucleocapsid antibody test results. Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti-CD-20 treatment, one - CAR-T cells and three underwent stem cell transplantation. The median duration of COVID-19 symptoms was 27.5 days (range 14-97); 12 patients had mild-to-moderate COVID-19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID-19 therapies before CCP. Within a median of two days (range 1-16) post-infusion, 19/20 patients clinically improved. No CCP-associated adverse events were documented. COVID-19 symptoms recurred in 3 of the improved patients. Two patients died from COVID-19 on days 1 and 90 following the first CCP infusion. In severely B-cell depleted patients with persistent COVID-19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration.

Outcomes of subsequent antilymphoma therapies after second-line axicabtagene ciloleucel or standard of care in ZUMA-7

AbstractThe optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = 59) was 6.3 vs 1.9 months, respectively; median OS was 16.3 vs 9.5 months, respectively. In the axi-cel arm, 84 of 180 randomized patients (47%) received 3L therapy. Median PFS among those who received 3L chemotherapy (n = 60) vs cellular immunotherapy (n = 8) was 1.7 vs 3.5 months, respectively; median OS was 8.1 months vs not reached, respectively. Of the 60 patients who received 3L chemotherapy, 10 underwent stem cell transplantation (SCT) after salvage chemotherapy. Median PFS was 11.5 vs 1.6 months, and median OS was 17.5 vs 7.2 months for those who did vs did not reach SCT, respectively. Eight patients received 3L cellular immunotherapy after 2L axi-cel. Of these, 6 patients received subsequent SCT in any line; all 6 were alive at data cutoff. These findings help inform subsequent treatment choices after 2L therapy failure for relapsed/refractory LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

TA-TMA Is Frequent, but Not All TA-TMA Is Actionable in Adult Allogeneic HCT Patients: A Report from the MIDAS (Microangiopathy, Endothelial Damage in Adults undergoing Stem cell transplantation) Consortium.

TA-TMA Is Frequent, but Not All TA-TMA Is Actionable in Adult Allogeneic HCT Patients: A Report from the MIDAS (Microangiopathy, Endothelial Damage in Adults undergoing Stem cell transplantation) Consortium.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Effectiveness of Intensive Chemotherapy with 7+3 Versus Vidaza and Venetoclax in Acute Myeloid Leukemia with Sequential Stem Cell Transplant: Results from Real-World Cohorts

Introduction: Intensive chemotherapy(IC) with cytarabine and anthracycline (7&amp;3) has been the backbone therapy for medically fit patients for the last 50 years. The use of Venetoclax and hypomethylating agent combination has be used in older and unfit patient populations. The Venetoclax combination regimen has improved outcomes in the selected group but has been characterized to be inferior to 7&amp;3 regimen among some studies. The role of stem cell transplant has not been previously discussed who receive IC versus Venetoclax based chemotehrapy Methods: Retrospective data was extracted using the TriNetX database. The primary endpoint was overall survival, and stem cell transplant in the two cohorts. Results: 5590 patients were identified in cohort-1 (7+3 cohort) and 2944 patients were identified in cohort-2 (Vidaza with Venetoclax cohort). Table-1 shows patient characteristics at baseline. Propensity-score-matching was used to balance the two cohorts. Patient count in each group after matching was 1393 (Table-2). Overall survival was 43.78% in cohort-1 versus 16.56 % in cohort-2, with HR of 0.510 (95% CI 0.457, 0.569) in favor of cohort 1 (Figure-1) at 5-year mark. Median OS for cohort-1 was 1055 days versus 289 days for cohort-2. Additional analysis was performed to determine number of patients who underwent a Stem Cell Transplant in each cohort and the effect of transplant on outcomes. 462 patients in cohort-1 and 358 patients in cohort-2 underwent transplant respectively. Overall survival was 51.29% in cohort-1 versus 61.64% in cohort-2, with HR of 1.180 (95% CI 1.027, 1.254) in favor of cohort-2 at 5-year mark. Median overall survival was not reached for either cohort at the data cut-off. Conclusions: Our retrospective analysis of a large patient cohort showed improved OS and decreased risk of death in patient's undergoing 7&amp;3 induction therapy as compared to Vidaza with Venetoclax. In patients who underwent stem cell transplant, the overall survival was statistically better in Vidaza with Venetoclax cohort as compared to 7&amp;3 induction therapy cohort. To the best of our knowledge, this is the first large database based study evaluating these two induction regimens accounting for stem cell transplantation.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes in Patients with Mantle Cell Lymphoma in China: A Retrospective Analysis Using a Real-World Database

Background: Significant advancements and novel therapeutic options have emerged in the treatment of mantle cell lymphoma (MCL) in recent years. However, there is a dearth of research on real-world treatment patterns, healthcare utilization, and costs associated with MCL in middle-income countries like China. Given that MCL predominantly affects the elderly population, this study aimed to assess the characteristics, treatment approaches, healthcare resource utilization (HCRU), costs, and survival outcomes in a representative sample of patients diagnosed with MCL in Tianjin City. Methods: This retrospective study utilized integrated regional electronic healthcare records spanning from 2004 to 2022. The sample included patients newly diagnosed with MCL who had a continuous series of healthcare encounters, with the index date set as the date of the initial MCL diagnosis. The study examined treatment patterns, all-cause and MCL-related HCRU and costs, as well as overall survival in both the initial treatment and relapsed/refractory settings. Results: The study identified 475 patients who had a confirmed diagnosis and met the specified inclusion/exclusion criteria. Overall, the patients with MCL had an average age of 58 at the index date, with 123 (25.9%) being female, and 139 (29.3%) having insurance coverage. The average Charlson Comorbidity Index (CCI) during the baseline period was 1.8 (SD:2.1), and the most prevalent comorbid conditions included hypertension (23.6%), pulmonary infection (21.9%) and diabetes (13.6%). A total of 250 (54%) patients had received treatment specific to MCL, with 57 (22.8%), 138 (55.2%), and 45 (18.0%) initiating chemotherapy, immunochemotherapy, and targeted therapy in first-line treatment, respectively. Among those who received targeted therapy,44 (50.0%), 40 (45.5%), 1 (1.1%) and 3 (3.4%) were treated with ibrutinib, zanubrutinib, orelabrutinib, and venetoclax, respectively. Additionally, 43 (9.1%) and 4 (0.8%) underwent stem cell transplantation and CAR-T therapy, respectively. Regarding HCRU, 367 patients (77.3%) experienced hospitalizations, with 328 (69.1%) of these hospitalizations related to MCL. Over the study period, the utilization of emergency department (ED) and outpatient services increased. The average monthly per person utilization rates for inpatient, outpatient, and emergency department visits were 0.62, 0.23, and 0.61, respectively. The mean total monthly healthcare costs were $9454.0 (inpatient), $895.9 (outpatient), $129.9 (ED), and $1739.0 (medication). The median overall survival (OS) from initiation of first-line (1L) treatment was 72.4 months, respectively. The 1-year and 3-year survival rates were 95.3 % and 86.9% from the initial diagnosis, and 78.6% and 71.4% from 1L treatment initiation, respectively. Conclusions: This real-world study, utilizing regional healthcare data, revealed distinctive demographic, clinical, and tumor-related characteristics among patients diagnosed with MCL. These patients demonstrated diversity in terms of age, insurance status, and healthcare resource utilization. As novel therapies continue to emerge, future investigations should address the unmet needs of patients with MCL, ensuring improved accessibility to innovative treatments.

Real-World Use of Hypomethylating Agents (HMA)/Venetoclax Combinations in Patients with Myelodysplastic Neoplasms (MDS) in the Arabian Gulf Region

Context: Retrospective data thus far has supported improved responses with HMA/venetoclax combinations in both the frontline and relapsed settings. A Phase Ib trial of azacitidine and venetoclax for high-risk MDS patients demonstrated an overall response rate (ORR) of 80%. Retrospective data from the Moffitt Centre comparing HMA/venetoclax to patients who received HMA showed an ORR of 77% compared to 40% for patients who only received HMA. Objectives: Our aim was to obtain real-world evidence for use of combination HMA/venetoclax to treat myelodysplastic patients in the Arabian Gulf region. Methods: This is a retrospective study of patients with myelodysplastic neoplasm treated with a HMA/venetoclax in 4 different countries from Jan 2020 - May 2023. Cases were included if they were over the age of 18, and had a diagnosis of MDS or MDS/AML. Both frontline and relapsed/refractory patients were included. Patients were excluded if they had more than 20% blasts or received an additional agent with their treatment. Results: Data on 16 patients was collected across 4 centres in the Arabian Gulf. The median age was 66 (range 51-84). All patients had high-risk MDS, MDS/AML including four patients with a TP53 mutation and/or complex cytogenetics. Median follow-up was 15 months (range 4-23). A median of 6 cycles were received (range 3-14). Azacitidine was the only HMA used at a starting dose of 75mg/m 2 for 7 days. Venetoclax starting dose was 400mg (or equivalent if given with an azole) and given for a median of 15 days (range 10-28). Thirteen patients received azole prophylaxis. Thirteen patients achieved a CR/CRi (81%), one patient who didn't had a TP53 mutation with complex cytogenetics, another had secondary MDS, and the third had stable disease and proceeded to transplant. Overall survival (OS) at 12 months was 86.2% (95% CI 55.0-96.4). For patients with poor risk disease (TP53 or complex cytogenetics) OS was 66.7% (95% CI 5.4-94.5) vs 90.9% (95% CI 50.8-98.7) for non-poor risk patients; p=0.006. Median OS was 22 months (22-NR) for non-poor risk patients compared to 14 months (10-NR) for poor risk patients. Event-free survival (failure, transformation or relapse) at 12 months was 84.6% (95% CI 51.2-95.9); it was 90.0% (95% CI 47.3-98.5) for those with no poor risk features and 66.7% (5.4-94.5) for those with poor-risk features; p=0.027. For those who stopped, 4/16 stopped due to failure and disease progression or transformation, 4/16 underwent stem cell transplantation, 3 stopped due to infectious complications, two from drug access issues, and one patient with secondary MDS had recurrence of their primary solid tumour. The most common toxicities were cytopenias and one patient died from cellulitis and COVID while on HMA/venetoclax. Conclusion: The combination of HMA/ venetoclax is a feasible treatment for patients with high-risk MDS with significantly worse outcomes in patients with complex cytogenetics and/or TP53 mutations. This regimen seems to be adapted by many hematologists in our region. However, the long-term efficacy in comparison to standard of care for various subgroups of MDS needs to be explored in larger prospective studies

Real World Clinical Characteristics, Treatment Patterns and Outcomes of R/R B-Cell ALL Adult Patients in Latin America

Introduction. Acute lymphoblastic leukemia (ALL) frequently affects mainly children and young adults. ALL has seen important progresses in diagnosis techniques and treatment approaches in the last decade. However, in some developing countries, there are inequalities in ALL management, such as heterogeneous access to diagnosis technologies (e.g., cytogenetic and molecular profiling) and access to target therapies treatments. To date, there is scarce data on those impacts in treatment patterns and real-world outcomes of adult relapsed/refractory (R/R) B-cell ALL (R/R ALL) patients in Latin America (LA). Therefore, this study aims to describe treatment patterns, clinical characteristics, and outcomes of R/R ALL adult patients treated in LA. Methods. This was a retrospective multicenter non-interventional study to evaluate treatment patterns, clinical characteristics and outcomes conducted in Argentina, Brazil, and Colombia. The study included patients ≥ 18 years old at diagnosis with confirmed R/R ALL between January 1, 2015, to December 31, 2019 that received at least one line of treatment for R/R ALL. Data collected from medical records was considered for the analysis, which was descriptive in nature, as no hypothesis has been tested. Results: A total of 71 patients diagnosed with R/R ALL were included in the study (23 from Argentina, 27 from Brazil, and 21 from Colombia). Table 1 shows the demographics and clinical characteristics. The median age at diagnosis was 31 years (Q1-Q3: 24.0-46.0), 56.3% were male, and 50% were White/Caucasian patients. At diagnosis, the most common comorbidities were diabetes, hypertension, gastrointestinal disease, and thyroid disease, with 11% each. At diagnosis, most patients presented with poor or intermediate cytogenetic risk prognosis, in 55.1% and 31.6%, respectively. Most of the patients presented with good performance status, 50.9% ECOG 0 and 36.8% ECOG 1. As for treatment patterns, patients received up to six treatment lines (LOT-1 to LOT-6), with a median of 2.0 LOTs (Q1-Q3: 1.5-3.0) within the R/R setting. Fifty-three (74.6%) out of the 71 patients enrolled in the study received two lines of R/R treatment (up to LOT-2), and 27 patients (38%) received 3 lines (up to LOT-3). The median treatment duration of LOTs were 3.4 months (Q1-Q3: 1.14 - 5.7), 1.4 months (Q1-Q3: 0.62 - 2.6) and 0.9 months (Q1-Q3: 0.4 - 2.1) for LOT-1, -2 and -3, respectively. The most frequently used treatment regimens at LOT-1 were the Hyper-CVAD (22.9%), BFM (20.0%) and GRAAL (15.7%). The most reported reasons for patients discontinuing their regimen in LOT-1 were progression of disease (37.5%), followed by adverse events (25%). For LOT-2 discontinuation, adverse events and/or toxicity (33.3%) were most frequently reported, followed by progression of the disease (25%). Of the total number of R/R ALL patients, 26 (36.6%) underwent stem cell transplantation (SCT), with a median time from diagnosis to transplantation of 9.6 months. All those patients (n=26) received allogeneic hematological SCT (100%), and haploidentical donors were most common (42.3%), followed by identical (matched) related (34.6%), mismatched unrelated donor (15.4%), and identical (matched) unrelated donors (7.7%). For R/R ALL patients, the median overall survival (mOS) was 18.96 months, with a probability of survival of 66.6% at 1 year, 32.3% at 3 years, and 16.2% at 5 years. Philadelphia Chromosome (Ph) molecular results were reported in 53 patients: 38 (71.7%) were Ph- and 15 (28.3%) were Ph+. The mOS in Ph+ patients was 31.5 months, numerically longer than the 17.7 months seen in Ph- patients (p = 0.500); however, the Kaplan-Meiers crossed over and separation was not clearly evident within the follow-up period (Figure 1). Conclusions: This study enabled a better understanding of R/R ALL in LA in the real-world. Data from this study demonstrate the high heterogenicity within first salvage (LOT-1) treatment patterns in R/R ALL, likely due to no established single standard of care in the region and highlights that only a fraction of the patients undergo SCT, which should be the treatment goal following induction therapy. In addition, our study reinforces already published data that overall survival on R/R ALL adult patients remain poor. Consistent guidelines and access to new treatments and are needed to remove inequalities in the management of ALL in LA.

Cladribine and Cyclophosphamide Lymphodepletion Prior to Brexucabtagene Autoleucel in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia and Mantle Cell Lymphoma

Introduction : Fludarabine and cyclophosphamide (Flu/Cy) lymphodepletion (LD) prior to chimeric antigen T-cell (CAR T) infusion favorably impacts CAR T expansion and efficacy. A national shortage of Flu prompted our center to explore substitute Flu with Cladribine (Cla) as part of Cla/Cy LD. Here, we report our experience with this regimen prior to brexucabtagene autoleucel (brexu-cel) for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and mantle cell lymphoma (MCL). Methods : We performed a retrospective, single-center analysis of consecutive patients who received brexu-cel for RR B-ALL and MCL at Moffitt Cancer Center (1/2022 and 4/2023). The Cla/Cy LD regimen utilized Cy at 500 mg/m 2 x 3 days for MCL or 900 mg/m 2 x 1 day for B-ALL (two patients received MCL dosing) and substituted Flu 30 mg/m 2 with Clad 5 mg/m 2 x 3 days. We compared best overall response (BOR), including measurable residual disease (MRD) status by the clonoSEQ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) ± PCR for B-ALL, event-free survival (EFS, event = progression or death) and overall survival (OS) in those receiving standard Flu/Cy vs Clad/Cy LD. CRS and ICANS were graded as per ASTCT criteria. For patients with a sustained response ≥6 months and who did not undergo stem cell transplant, we assessed serial absolute neutrophil counts (ANC), CD4, CD8, CD19 counts and IgG levels post-CAR T. The HEMATOTOX score (HS, Rejeski et al, 2021) was used to stratify patients for risk of post-CAR T cytopenias. Results : We analyzed 63 patients who received brexu-cel: 23 with ALL (10 Cla/Cy) and 40 with MCL (7 Cla/Cy). Rates of CRS grade ≥ 3 (12% vs Flu/Cy 4%; p=0.29) and ICANS grade ≥ 3 (24% vs Flu/Cy 40%; p = 0.25) did not differ with LD. Two ALL (1 Flu/Cy, 1 Clad/Cy) and one MCL (Flu/Cy) patients died prior to day 28 reassessment. BOR did not differ by LD and histology (Figure 1). MRD negativity in ALL was also comparable (Cla/Cy 5/7, Flu/Cy 10/11, p=0.52). Among ALL patients, 5 received alloSCT consolidation (1 Cla/Cy). Progression was noted in 3/8 Cla/Cy and 6/11 Flu/Cy patients (p=1.0). Fifteen ALL patients experienced early infections (6/10 Cla/Cy, 9/13 FluCy, p=0.69), including bacterial (5), viral (4), and fungal (3). Three deaths (2 Cla/Cy) occurred before day 100, all due to refractory fungemia post anakinra. Two later deaths were attributed to relapse (both Flu/Cy). Among MCL patients, progression was noted in 16 (1 Cla/Cy). Seven MCL patients experienced early infection (all Flu/Cy), including bacterial (6), fungal (2), and viral (1). Two deaths occurred before day 100, 1 related to CRS and fungemia post anakinra (Flu/Cy), and another from stroke (Cla/Cy). Four (all Flu/Cy) have developed a second cancer (2 MDS/AML, 1 prostate, 1 liver), and 1 each died in remission from late infection (sepsis) and intracranial hemorrhage (both Flu/Cy). Cla/Cy patients had higher median ANCs at 28, 90, and 180 days (Table 1). When only patients with HS ≥ 2 were considered, 28-day ANC remained higher after Cla/Cy LD (1.57 vs Flu/Cy 0.67; p=0.04), numerically higher at 90 days (2.36 vs Flu/Cy 1.82; p=0.38) and again significantly higher at 180 days (3.96 vs Flu/Cy 1.2; p=0.05). Median CD4 was higher for Cla/Cy patients at day 28 (0.232 vs Flu/Cy 0.121; p=0.04), and numerically higher at day 90 (0.244 vs Flu/Cy 0.152; p=0.31) and 180 (0.254 vs Flu/Cy 0.161; p=0.21). Median CD8 was similar at day 28 (0.197 vs 0.155; p=0.46), 90 (0.435 vs Flu/Cy 0.167; p=0.65), and 180 (0.557 vs 0.220; p=0.14). There was no difference in IgG levels at day 28 (502 vs Flu/Cy 466; p=0.87), 90 (385 vs Flu/Cy 393; p=0.76), or 180 (424 vs Flu/Cy 426; p=0.94). Median CD19 was greater for Cla/Cy at day 90 (median 0.095 vs 0.000; p&amp;lt;0.01) and numerically higher at day 180 (0.213 vs Flu/Cy 0.000; p=0.29). Median duration of followup was 245d for ALL (FluCy 361d, ClaCy 194d) and 746d for MCL (FluCy 812d, ClaCy 215d). Median DOR, EFS, and OS did not differ by LD (Figure 1). Conclusions : Cla/Cy LD prior to brexu-cel is feasible in ALL and MCL patients with comparable efficacy. Toxicity rates including CRS, ICANS and early infections were similar to those seen with Flu/Cy, but there was a trend towards earlier recovery of neutrophils, B-, and T-cells with Cla/Cy. The trend was demonstrable even in patients at high risk of prolonged post-CAR T neutropenia as identified by the HS. Longer follow-up and correlative analyses are warranted to further explore differences between Cla/Cy and Flu/Cy.

Outcome of Infants Treated on Total Therapy for Infants with Acute Lymphoblastic Leukemia I: Results from a Non-Randomized Multi-Center Study

Infants with KMT2A rearranged (KMT2Ar) acute lymphoblastic leukemia (ALL) have a poor prognosis with an event-free-survival (EFS) of 33.6-36.9% on recent Children's Oncology Group and Interfant trials. In preclinical studies, we identified bortezomib and vorinostat as novel active agents in primary KMT2Ar infant ALL specimens that have not been included in infant regimens to date. Total therapy for infants with acute lymphoblastic leukemia I (TINI) evaluated this novel combination in a multi-institutional pilot trial for infants with de novo ALL. In this study, bortezomib and vorinostat were incorporated into an ALL chemotherapy backbone containing dexamethasone, mitoxantrone, and pegasparaginase during induction and reinduction chemotherapy cycles. A run-in dose escalation evaluated 3 dose levels of vorinostat which was then followed by a dose expansion phase. The primary endpoint of the study was tolerability; secondary endpoints included minimal residual disease (MRD), 3-year EFS and overall survival (OS). Fifty patients enrolled between 2017-2021. Median follow up was 3.4 years (range 1.6-6.8 years). The six patients in the dose escalation phase had no dose-limiting toxicities. Forty-four patients received vorinostat at the third dose level (DL3) of 180 mg/m 2/dose. 68% of patients treated at DL3 had CNS involvement at diagnosis. 68% of DL3 patients carried a KMT2Ar. The most frequent KMT2A partner genes were AFF1 (40%), MLLT1 (20%), and MLLT3 (13%). The most frequent grade 3-4 non-hematologic adverse events during induction include neutropenic fever (45%), hypertension (43%), infection (40%), anorexia (32%), diarrhea (18%) and perineal skin ulceration (16%). There were 3 episodes of sepsis and 1 induction death due to parainfluenza pneumonia. Fewer events and no deaths or proven sepsis occurred during reinduction, with only grade 3 hypertriglyceridemia exceeding 10% of patients affected (18%). 79% of all patients and 69% of KMT2Ar patients became MRD negative by flow cytometry on day 22 of induction following our investigational block. Following induction intensification with cyclophosphamide, cytarabine, and mercaptopurine, 77% and 66% of all patients and KMT2Ar patients respectively were MRD negative at the time of count recovery. Eight of the forty-four patients, all KMT2Ar, underwent stem cell transplant in first remission due to persistent MRD positivity at the end of consolidation. The 3-year EFS and OS probabilities (SE) of all forty-four DL3 patients were 56.5% (8.0) and 70.5% (7.3), respectively. The 3-year cumulative incidence of relapse (CIR) with death considered a competing event was 29.3% (6.9) and the cumulative incidence of death (CID) as a first event was 8.9% (4.5). Patients lacking a KMT2Ar had superior outcomes with 85.7% (9.4) EFS and 92.9% (6.9) OS. The EFS and OS of KMT2Ar patients were 44.8% (9.5) and 62% (9.1) respectively. CIR and CID for KMT2Ar patients was 43.5% (9.6) and 7.2% (5) respectively. KMT2Ar patients ≥90 days at diagnosis had superior outcomes compared to their younger counterparts with 59.1% (10.5) EFS and 77.3% (8.9) OS. End of induction MRD was predictive of an event in this subgroup, with 85.6% (9.4) EFS for MRD negative patients and 14.3% (13.2) EFS for MRD positive patients. In contrast, KMT2Ar patients &amp;lt; 90 days of age at diagnosis had poor outcomes irrespective of MRD with 12.5% (11.7) EFS and 25% (15.3) OS. Notably KMT2Ar patients &amp;lt; 90 days who were MRD negative at the end of induction had a median time to relapse of 600 days (range 282-969 days), a late time point for this malignancy that typically relapses within a year from initial diagnosis. This suggests the regimen effectively reduced tumor burden leading to an extended duration of remission but failed to sufficiently eradicate disease to prevent relapse. We conclude that the incorporation of bortezomib and vorinostat for treatment of infants with ALL was well tolerated. MRD responses in KMT2Ar patients were robust. Although the study was not powered to evaluate outcomes, EFS and OS in KMT2Ar patients suggest a clinical signal worth pursuing given the low proportion of patients transplanted in first remission. The successor study, TINI 2 (NCT05848687), will build upon the bortezomib/vorinostat backbone by incorporating 2 cycles of blinatumomab and the menin inhibitor ziftomenib in combination with chemotherapy during reinduction.

Age-Based Comparison of Stem Cell Transplantation during the First Line of Therapy for Multiple Myeloma Patients

Background High-dose chemotherapy followed by stem cell transplantation (SCT) has been the standard first-line therapy for eligible multiple myeloma (MM) patients for over three decades. However, most studies evaluating SCT in MM have focused on patients under 65 years old, despite the increasing number of older patients diagnosed with MM. Retrospective data suggest that SCT can offer good survival outcomes with acceptable toxicities in patients over 65. This registry retrospective study aims to compare the time to next treatment (TTNT) of SCT versus non-SCT treatments in MM patients, assessing those aged &amp;lt;65 and ≥65 years old. Methodology Using HealthTree Cure Hub for Multiple Myeloma (PMID: 35271305), we analyzed real-world data from 1279 patients with multiple myeloma. Patients were categorized into two groups based on age at the start of their first line of therapy (&amp;lt;65 and ≥65). Kaplan-Meier ‘Time to Next Treatment’ (TTNT) R analysis was employed to compare patients who underwent stem cell transplant (SCT) and those who did not (NSCT) within each age group. SCT patients received a high-dose melphalan preparative regimen (140-200 mg/m2). Age groups were also subclassified by high-risk cytogenetics, using mSMART staging by fluorescence in situ hybridization (FISH), and Revised International Staging System (R-ISS) stage. Chi-square tests were used to assess the association with R-ISS and mSMART stages. Results We analyzed the data of 1279 MM patients, of whom 830 (64.9%) were &amp;lt;65 and 449 (35.1%) were ≥65. The &amp;lt;65 group had a mean age of 55±7, whereas the group ≥65 had a mean age of 70±5. 52.5% were female. The majority of patients were White (78.2% in the &amp;lt;65 group and 81.77% in ≥65), with other relevant groups including Blacks (5.8% in the &amp;lt;65 group and 4.2% in the ≥65 group), and Hispanics or Latinos (4.0% in the &amp;lt;65 group and 2.8% in the ≥65 group). The median year of diagnosis was 2018 (2006-2022).R-ISS staging was available for 664 patients and not dissimilar between groups ( p = 0.69): in the &amp;lt;65 group, 159 (37.2%) patients were classified as R-ISS stage I, 188 (44.0%) patients stage II, and 81 (18.9%) patients stage III. In the ≥65 group, 81 (34.3%) were stage I, 118 (50.0%) stage II, and 37 (15.7%) stage III. 1196 patients had mSMART staging available, of whom, patients with high-risk, double, and triple hit, represented 15.9%, 4.6%, and 0.4%, respectively. Age group high-risk characteristics proportions were not dissimilar ( p = 0.7). In the &amp;lt;65 group, 69.2% had a transplant during their first line of therapy, while in the ≥65 group, 48.8% had a transplant. For patients aged &amp;lt;65, the mean TTNT was 32.5 mo (SD 25) in the SCT group, and 16 mo (SD 21.6) in the NSCT group. For patients aged ≥65, the mean TTNT was 28.6 mo (SD 18.9) in the SCT group, and 16.5 mo (SD 18.3) in the NSCT group. The TTNT survival at 4 years was significantly higher in patients that experienced an SCT in both groups, &amp;lt;65 (SCT=40%, NSCT=18%, p = &amp;lt;0.0001) and ≥65 (SCT=43%, NSCT=14%, p = &amp;lt;0.0001). Conclusions Our findings add to the compelling evidence that SCT demonstrates favorable outcomes in both age groups of MM patients. The mean TTNT difference of SCT vs NSCT observed in the &amp;lt;65 group is 16.5 mo, and in the ≥65 group, it is 12.1 mo. Furthermore, patients who underwent SCT in both age groups had significantly higher TTNT survival rates at 4 years, doubling the rates to 40% in the &amp;lt;65 group and 43% in the ≥65 group, emphasizing the substantial benefits of SCT as a first-line therapy for multiple myeloma. These results contribute to the growing body of evidence supporting the efficacy and acceptability of SCT in the management of multiple myeloma across all age groups. It also emphasizes the importance of considering SCT as a viable treatment option for eligible MM patients, including those aged 70 and above, to improve long-term outcomes.

Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia

Background Blinatumomab improves overall survival (OS) compared with chemotherapy in patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and is also FDA-approved for eradication of persistent or recurrent measurable residual disease (MRD). Blinatumomab also improves OS when added to standard chemotherapy, irrespective of MRD status, in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL. Inotuzumab ozogamicin (INO) improves OS in the relapsed/refractory setting, and we hypothesized that the addition of INO to hyper-CVAD plus blinatumomab would lead to deeper and more durable responses, reduce relapses, and improve survival. Methods In this phase II study, pts age 14-59 with newly diagnosed Ph-negative B-cell ALL, including pts who had received no more than 1 prior cycle of chemotherapy, were eligible. Pts had to have a performance status of ≤3, total bilirubin ≤2 mg/dl, creatinine ≤2 mg/dl, and no significant CNS pathology (except for CNS leukemia). Pts received hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2). Eight doses of prophylactic IT chemotherapy were given. Maintenance was with alternating blocks of POMP (given in maintenance cycles 1-3, 5-7, 9-11, and 13-15) and blinatumomab (given in maintenance cycles 4, 8, and 12). Those with high-risk disease features started blinatumomab after 2 cycles of hyper-CVAD. Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C (which was also dose reduced to 500 mg/m2 of MTX and 1 g/m2 of Ara-C with this amendment) and to 2 cycles of blinatumomab consolidation (4 total cycles with INO). Results As of June 2023, 75 pts have been treated (38 without INO and 37 with INO). Pt characteristics are shown in Table 1. The median age across both cohorts was 33 (range, 18-59). 36 pts (48%) had ≥1 high-risk pretreatment characteristic at enrollment (e.g. poor-risk cytogenetics, CRLF2 overexpression by flow and/or TP53 mutation). Sixteen pts were in complete remission (CR) at enrollment after 1-2 cycles of off-protocol therapy, 10 of whom were MRD-negative by 6-color flow cytometry. All 59 pts (100%) with active disease upon study entry achieved CR, with 50 pts (84%) achieving CR after the first cycle. MRD negativity by flow (sensitivity 10 -4) was achieved in 60 of 65 evaluable pts (92%), with 43 pts (66%) achieving flow MRD negativity after the first cycle. Two of the 5 patients who did not achieve flow MRD negativity had NUP214::ABL1 fusion, 1 had KMT2A rearrangement, and 2 are still early in treatment and have not yet received blinatumomab. Overall, 25 of 36 tested pts (69%) achieved next-generation sequencing-based MRD negativity at a sensitivity of 10 -6. The median duration of follow-up is 26 months (range, 1-77 months). Overall, 8 pts (11%) relapsed in the absence of SCT, 23 pts (31%) underwent stem cell transplantation (SCT) in first remission (2 of whom relapsed post-SCT), 3 pts (4%) died in CR, and 41 pts (55%) remain in continuous remission without SCT. Among the 10 relapses, 3 were in the CNS, 2 of which were CNS-only. All but one relapse occurred in pts with ≥1 poor-risk feature(s). Across both cohorts, the estimated 3-year OS was 88% and the 3-year relapse-free survival (RFS) was 79% . The 3-year OS rate for pts without a high-risk baseline feature was 93% vs 83% in pts with ≥1 high-risk feature. In a landmark analysis, there was no difference in outcomes between pts who underwent SCT in first remission versus those who did not (3-year OS: 90% versus 87%). With a median follow-up of 18 months in the INO group, 3 pts (8%) have relapsed, 2 with CNS-only relapses, and none have died. The 18-month RFS in the cohorts with and without INO were 92% vs 76% (p=0.18), and the OS was 100% vs 84% (p=0.04) ( Figure 1). One pt discontinued blinatumomab due to a related adverse event (grade 2 encephalopathy and dysphasia). No pts discontinued INO due to toxicity, and no cases of veno-occlusive disease have been observed.

High Dimensional Clustering and Identification of Immune Cell Hybrid Populations in B-ALL across the Disease Continuum

Introduction: Nearly half of adults with acute lymphoblastic leukemia (ALL) will experience relapse of their disease, and those with relapsed ALL carry a worse prognosis than those who remain in remission. The influence of the tumor immune microenvironment (TME) on relapse and survival outcomes in ALL is not well understood. Mass cytometry (CyTOF) enables immune profiling based on single cell protein expression and can identify phenotypic diversity of cells in the TME that cannot reliably be detected by standard flow cytometry. Recently, T-cell/monocyte hybrid cells have been discovered in patients with uveal melanoma and latent tuberculosis infections. However, cells expressing CD19, a surface antigen expressed on B-ALL cells, and markers of other cells in the TME including T cells and tumor-associated macrophages (TAMs), have not been described in ALL or other hematologic malignancies. The presence of CD3/CD163 hybrid cells in the TME may have predictive and prognostic implications for adults with ALL, as TAMs play a role in suppressing antitumor immunity which can lead to T-cell exhaustion. In this study, we identify the presence of multilineage hybrid cells in peripheral blood (PB) and bone marrow (BM) samples of patients with B-ALL alongside accompanying evolution of the TME at each disease stage. Methods: PB (N=16) and BM aspirate (N=16) isolates were collected from patients with B-ALL at diagnosis, relapse, or remission, as well as from healthy donors (HDs, N=7) for comparison of cellular profiles. A 28-marker CYTOF panel was designed to evaluate cell surface and intracellular markers of interest in the myeloid compartment. Antibodies were purchased pre-conjugated or conjugated in house based on manufacturer guidelines (Standard BioTools). Samples were barcoded with palladium isotopes prior to staining to reduce the impact of batch effect, and were then analyzed on a first generation CyTOF system (Standard BioTools). Following background attenuation and singlet gating in FlowJo (BD), the CATALYST R package enabled deconvolution and visualization of single cell data, including dimensional reduction techniques (tSNE) and clustering of all cell populations. An iterative approach was taken to determine a stable configuration of clusters across sample populations to protect from over-fragmentation of data, further informed by K-means clustering using the elbow method. Heatmaps were then generated based on median scaled expression of markers contained in each cluster. Results: The CyTOF panel identified several different myeloid cell populations in newly diagnosed, relapsed, and remission samples in both PB and BM compared to HDs. Most interestingly, quantifiable levels of a cluster of cells co-expressing CD19, CD3 and CD163 as well as a second cluster of cells expressing CD19 and CD163 were detected in newly diagnosed and relapsed patients, but not in HDs. A single patient with the largest proportion of these cell populations in their PB at the time of relapse presented with an aggressive leukemia variant and relapsed multiple times prior to succumbing to illness. On investigation of BM aspirates, the triple positive hybrid population was found in a similar distribution amongst the newly diagnosed and relapsed patients, as well as affecting one patient who achieved remission. This patient also had a highly aggressive leukemia that was refractory to chemotherapy and immunotherapy, and only achieved this remission following CAR-T cell therapy. She subsequently underwent stem cell transplant and is in remission. Conclusions: Our findings add to the literature highlighting the utility of high parameter single cell capture techniques in detecting rare cell populations in the leukemic TME. Further, we identified two unique hybrid cell populations that are reliably detected across different disease stages in patients with B-ALL. Importantly, these populations persisted following stringent gating protocols to rule out doublets and debris. Although our sample size was too small to demonstrate a prognostic impact of these hybrid cell populations in patients with B-ALL, the identification of these populations alone is a significant finding. Further investigation and patient sample accrual are warranted to better understand the role of these cell types in tumor biology, which may pave the way towards new prognostic models that can leverage well-established immune monitoring techniques.

Real-World Study in Acute Leukemia: Epidemiology, Treatment Patterns and Outcomes for Newly Diagnosed AML in Adult Patients from Latin America - Loyal Study

Introduction. Acute myeloid leukemia (AML) is the most frequent leukemia among adults and representing 90% of all cases of acute leukemia in adults. Differences in incidence and burden of AML among regions of the world have been reported. When compared with registries from the US, UK and Sweden, Latin-America (LA) AML has a younger age at diagnosis (median age of 40-47 versus 64 -67 years old). Furthermore, single center studies have suggested poor treatment outcomes in LA. For example, Silveira et al reported a median age at diagnosis of 46 y, frequency of favorable cytogenetics of 26% and median overall survival (mOS) of 12 months in the Brazilian cohort of patients with newly diagnosed AML (nAML) whereas the respective values at Oxford University were 51.5y, 11% and 48 months in British patients. However, wider studies across the region are scarce and there is a need to further explore AML patient characteristics and treatment outcomes in LA. Methods. This is a non-interventional, retrospective multicenter study that aims to describe the epidemiology, clinical and demographic characteristics, treatment patterns, survival outcomes and healthcare resource use of adult patients with nAML in Argentina, Brazil, Chile, and Colombia. Data from medical records of eligible patients that met the inclusion criteria (≥ 18 years old at diagnosis, confirmed diagnosis of nAML between 01 January 2015 and 31 December 2019, and receiving at least one line of treatment) in these LA countries were considered for the analysis, which was descriptive in nature as no hypothesis has been tested. Results: A total of 518 nAML patients were included in the study, 166 from Argentina, 205 from Brazil, 63 from Chile, and 84 from Colombia. Table 1 shows the demographics and clinical characteristics. At treatment initiation, an evaluation of fitness (eligibility) for intensive chemotherapy was available for 94% of the patients (n=489). The majority were considered fit (75.5%; n=391) and received standard 7+3 therapy. About 11% of patients (n=9) were refractory to induction therapy. Median OS for fit patients was 11.9 months, whereas for unfit patients was 5.8 months. Mutational status of genes listed by the European LeukemiaNet (ELN) Classification of 2017 was not available for the majority of cases; risk categories were assigned based on cytogenetics. Patients in the favorable-risk category had a mOS of 30.5 months, whereas those in the intermediate- and unfavorable-risk had 11.1 and 9.1 months, respectively (Figure 1). The probability of 5year OS rates for favorable, intermediate- and unfavorable-risk groups were of 38.8%, 16.6% and 20.9%, respectively. Eighty-six patients (17%) discontinued treatment with reasons being adverse event/toxicity (33%; n=28), death (32%; n=27), and disease progression (17%; n=14). Only 24% of patients (n=125) underwent a subsequent stem cell transplantation (SCT), mainly allogenic (98%; n=121). For SCTs, identical (matched) related (50%; n= 59) and haploidentical donor (35%; n=41) were the most common. Patients not eligible to intensive chemotherapy were treated with HMA (9%; n=47) and LDAC (5%; n=25), with 10% of the patients receiving palliative/supportive care. The most common treatment protocols used in relapsed or refractory (R/R) patients were high-dose cytarabine (HDAC) (31%; n=85), followed by FLAG-IDA (24%; n=66). Conclusions: This study of newly diagnosed acute leukemia characterizes real-world treatment patterns and outcomes in LA clinical practices. Prior to this study, there has been limited published data on the epidemiology and treatment patterns across LA. This study highlights that for nAML patients, the most common treatment in LA is 7+3 and most patients are classified as fit. The vast majority of patients had their risk accessed by cytogenetics analysis only, reflecting the limited access to molecular tests. Fewer patients underwent stem cell transplantation as part of the treatment compared to that reported in US and Europe, probably due to restricted availability of hospital beds dedicated to bone marrow transplantation. When evaluating the overall survival, the study shows higher mOS for favorable risk. In addition, mOS for intermediate and poor cytogenetic risk were similar. A broader access in the region to molecular tests, transplant and new therapies are needed in order to reduce the gap in outcome, especially for patients with intermediate-risk.

ABO Incompatibility Haploidentical Peripheral Blood Stem Cell Transplantation Combined with a Single Cord Blood Unit for Severe Aplastic Anemia Patients

Background: For young severe aplastic anemia (SAA) patients without HLA matched donors, haploidentical hematopoietic stem cell transplantation can be used as an alternative selection. The grafts of classic Beijing protocol in China is a combination of bone marrow and peripheral blood stem cell. For patients with major or minor blood type incompatibility, bone marrow stem cells need to undergo red blood cell or plasma removal treatment. There was rare reports about haploidentical peripheral blood stem cell combined with a single unrelated cord blood unit for ABO incompatibility haploidentical stem cell transplantation in SAA patients. Objective: To observe the efficacy of ABO incompatibility haploidentcial peripheral blood hematopoietic stem cell transplantation combined with a single unrelated cord blood unit for SAA patients. Method s : Fifty-five SAA patients underwent stem cell transplantation from August 2018 to February 2022 in the First Affiliated Hospital of Xi'an Jiaotong Univeristy were divided into two groups based on donor-recipient ABO compatibility, the donor-recipient ABO matched group（BM+PB group）using haploidentical bone marrow and peripheral blood stem cell as grafts, and donor-recipient ABO mismatched group（CB+PB group）, using unrelated cord blood and haploidentical peripheral blood stem cell as grafts. The differences of hematopoietic reconstitution, acute and chronic GVHD, CMV and EB virus infection, PFS, and OS between the two groups were compared. Result s : There were 30 cases in CB+PB group and 27 cases in the BM+PB group. Except for differences in donor-recipient ABO compatibility, the other characteristics of the two groups of patients were comparable((P&amp;gt;0.05). One patient in the BM+PB group had primary graft failure, while the rest of the patients were successfully implanted. There were no significant statistical differences in neutrophil,platelet and red blood cells recovery rates, the incidence of acute and chronic GVHD, CMV, EB virus infection, and PTLD between the two groups of patients(P&amp;gt;0.05). There was no significant statistical difference in OS between the two groups of patients(P&amp;gt;0.05)(Figure 1). Conclusion: For SAA patients with donor-recipient ABO incompatibility could use haploidentical peripheral blood cell combined with unrelated cord blood for transplantation which had compared outcome with haploidentcal bone marrow and peripheral blood cell transplantation.