Use Of Total Body Irradiation Research Articles

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia: Results of a Single-Center Study.

Despite the adoption of pediatric-like chemotherapy protocols, the introduction of new immunotherapies and a better understanding of the oncogenic landscape, the outcome for adult patients with acute lymphoblastic leukemia (ALL) remain substantially dismal. The aim of the present study was to evaluate the outcome in terms of survival in a cohort of adult patients with ALL who received allogeneic hematopoietic stem cell transplantation (alloSCT) between 2013 and 2023. This was a single-center observational retrospective study including all consecutive adult patients with ALL who received an alloSCT between April 2013 and April 2023 at the Stem Cell Transplant Center AOU Città della Salute e della Scienza of Torino. The primary endpoints were overall survival (OS), graft-versus-host disease (GVHD) Relapse-Free Survival (GRFS), Leukemia-Free Survival (LFS) and cumulative incidence (CI) of Non-Relapse Mortality (NRM). The 4-year OS and LFS were 63.4% and 48.1%, respectively, and the 1-year GRFS was 42.9%. The 1-year CI of bloodstream infections (BSI), invasive fungal infections and NRM were 38%, 7% and 18.4%, respectively. Multivariate analysis showed that the use of total body irradiation (TBI), a time interval from diagnosis to alloSCT 7 months and female gender were factors significantly associated with better OS. Relapse of the underlying malignancy and BSI were the main causes of death. Our study suggests that alloSCT from a matched sibling donor (MSD) and alternative donors may be considered an effective tool for patients with ALL achieving a CR.

Infection-Related Mortality in Children Undergoing Hematopoietic Stem Cell Transplants at a Referral Center in Mexico

Abstract Background Infections constitute a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, infection-associated mortality rate ranging from 7% to 17% has been reported, depending on the type of HSCT, being lower in autologous transplants and higher in cases involving unrelated donors. Other factors related to HSCT that influence the clinical outcomes of these patients include the intensity of the conditioning regimen, the development of graft-versus-host disease (GVHD), cytotoxic and immunosuppressive effects of the medications used, the presence of disease activity prior to HSCT, length of hospital stay, and the use of intravascular devices, among many others. Methods All pediatric patients (under 16 years old) undergoing HSCT at the ‘Dr. José Eleuterio González’ University Hospital over a 55-month period (March 2019 – October 2023) were included. Clinical and epidemiological characteristics of the patients, mortality rate, and risk factors related to transplantation and infectious events (IEs) in these patients were recorded. Results A total of 75 patients who received HSCT were included, among them, 52 patients (69%) presented IEs. The mortality associated with IEs among these patients was 6% at day 30 and 12% at day 100, compared to 0% and 1.3% respectively in the non-IEs related deaths. The epidemiological characteristics, baseline diagnosis, donors and graft source are described in table 1. The average number of IEs in the associated mortality cases was 2.8 compared to 1.6 in the survival group. Among the mortality group (8 cases), 67% presented multiple infections and 33% single infections, with a 75% of them caused by viral infections. Regarding HSCT characteristics, in the group with IE-associated mortality, a higher proportion of haploidentical transplants, myeloablative conditioning regimens, lower use of total body irradiation, and a higher proportion of patients with detectable disease by flow cytometry prior to HSCT were observed compared to the survival group. Among non-infectious complications related to HSCT a lower frequency of acute GVHD grade I-II, a higher frequency of acute GVHD grade III-IV in the IE-associated mortality group was identified. Among the risk factors associated with hospital care, the IE-associated mortality group showed a higher use of central venous catheters, mucositis, systemic steroids, and pediatric intensive care unit stay compared to the survival group. Conclusion Pediatric patients undergoing HSCT present multiple risk factors that increase the incidence of infectious events and contribute to higher mortality rates. It is crucial to identify those factors related to adverse events and death to implement strategies that reduce exposure to these factors and improve the clinical outcomes.

Late-Onset Noninfectious Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation: Single-Center Experience.

We aimed to reveal the incidence of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome and risk factors involved in development. In this cross-sectional study, we retrospectively investigated 745 patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between January 2000 and December 2020. We evaluated demographic characteristics, comorbidities, and hematopoietic stem cell transplantation characteristics to determine possible risk factors affecting development of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome. Of 745 patients, 8.9% (n = 66) had late-onset noninfectious pulmonary complications. Complications included 38 patients with bronchiolitis obliterans syndrome, 13 with venous thromboembolism, 8 with cryptogenic organizing pneumonia, 5 with pneumothorax, 4 with interstitial lung disease-restrictive graft-versus-host disease, 5 with bronchiectasis, 2 with pneumomediastinum, and 1 with pleural effusion. Patients with and without complications were not significantly differentin terms of smoking history, hematopoietic stem cell transplantation characteristics, and conditioning regimens. Patients with complications had higher busulfan and lower antithymocyte globulin use than those without complications (both P<.05). Patients with complications more commonly had hematopoietic stem cell transplantation from related donors and chronic graft-versus-host disease (P < .05). Patients with bronchiolitis obliterans syndrome had more frequent use of busulfan (P <.05) but less frequent use of total body irradiation (P <.05) and antithymocyte globulin (P <.05) than those without this syndrome. Rate of hematopoietic stem cell transplantation from a related donor (P < .05) and frequency of chronic graftversus-host disease (P < .001) were significantly higher in patients with bronchiolitis obliterans syndrome, presented with bronchiectasis (78.6%), air trapping (67.9%), bronchial wallthickening (53.6%), and mosaic attenuation (39.3%) in thorax computed tomography. Pretransplant spirometry did not predict bronchiolitis obliterans syndrome development. Determining risk factors for late-onset noninfectious pulmonary complications is needed to aid in prevention and follow-up.

Outcomes of Hematopoietic Cell Transplantation for Patients with Refractory Cytopenia with Multilineage Dysplasia: A Comparison Children with Adolescents and Young Adults

Background: The 2008 World Health Organization (WHO) classification proposed a new entity in childhood myelodysplastic syndrome (MDS), refractory cytopenia of childhood (RCC). The spectrum of patients with RCC is wide, ranging from patients with severe hypocellular bone marrow (BM) and mild dysplasia (hypocellular RCC) to those with normocellular BM and distinct dysplasia meeting the criteria for refractory cytopenia with multilineage dysplasia (RCMD) defined for adults with MDS. The term of RCMD was revised to MDS with multilineage dysplasia in the 2017 WHO classification. In Japan, children who meet the criteria for RCMD have been diagnosed as RCMD distinguished from hypocellular RCC. Although hematopoietic cell transplantation (HCT) is a curative treatment for RCMD in children, there have been few reports of the outcomes of HCT for children with RCMD. Patients and Methods: To clarify the outcomes of HCT for children with RCMD, we retrospectively analyzed the clinical data in children (&amp;lt;16 years) with RCMD who underwent the first HCT from 2010 to 2021 and registered in the Japan Society for Hematopoietic Cell Transplantation Registry, and compared with those in adolescents and young adults (AYA; ≥16, &amp;lt;40 years) with RCMD who underwent the first HCT during the same study period. During the study period, 195 patients with RCMD (children, 69; AYA, 126) underwent HCT. The stem cell source was BM in 138 (children, 58; AYA, 80), peripheral blood (PB) in 27 (children, 2; AYA, 25), and cord blood (CB) in 30 patients (children, 9; AYA, 21). Myeloablative conditioning (MAC) regimen was defined as the use of total body irradiation (TBI) ≥8 Gy (MAC-TBI) and the administration of busulfan (BU) &amp;gt;8 mg/kg (MAC-BU). All other regimens were included in reduced intensity conditioning (RIC) regimen. Results: We retrospectively analyzed 195 patients with RCMD (male, 105; female, 90). The median age at HCT was 8 years (range, 0-15) in children and 29 years (range, 16-39) in AYA. Of the 195 patients, 20 (29%) and 52 (41%) had abnormal karyotypes in children and AYA, respectively. Of the patients who underwent HCT, 68 were from related (children, 22; AYA, 46), and 127 from unrelated (children, 47; AYA, 80) donors. MAC-BU was used for 46 (children, 9; AYA, 37), MAC-TBI for 51 (children, 1; AYA, 50), and RIC for 98 (children, 59; AYA, 39) patients. Of the 195 patients, 8 (children, 3; AYA, 5) developed primary graft failure, 16 (children, 5; AYA, 11) secondary graft failure, 10 (children, 3; AYA, 7) disease relapse, and 11 (children, 2; AYA, 9) secondary tumor. Twenty-four (children, 5; AYA, 19) patients died of HCT-related complications and four AYA of disease relapse. The 5-year overall survival (OS) rate was significantly higher in children (93%) than in AYA (82%) (p = 0.04). The 5-year event-free survival (EFS) rate was 76% in children and 64% in AYA. The 1-month cumulative incidence (CI) of neutrophil engraftment was 93% in children and 94% in AYA. The 5-year CI of relapse was 6% in AYA and 2% in children. The 5-year CI of treatment-related mortality (TRM) was 16% in AYA and 7% in children. The 5-year CI of graft failure was 12% in children and 12% in AYA. The 3-year CI of chronic graft-versus-host disease (GVHD) was significantly higher in AYA (37%) than in children (21%) (p = 0.04), while there was no difference in the 3-month CI of acute GVHD (gradeⅡ-Ⅳ) between children (35%) and AYA (39%). In children, the 5-year OS and EFS rates were significantly lower in CB (67% and 42%) than in BM/PB (97% and 81%) (p &amp;lt; 0.01 and p &amp;lt; 0.01), respectively, while the 5-year OS and EFS rates were not different between CB (91% and 76%) and BM/PB (80% and 62%) in AYA, respectively. Of the 59 children who underwent HCT using RIC, 43 without abnormal karyotypes showed 95% and 16 with abnormal karyotypes showed 88% in the 5-year OS rate. Even in AYA, there was no difference in the 5-year OS rate between RIC and MAC in both groups with (RIC, n = 14, 76%; MAC, n =38, 72%) and without (RIC, n = 25, 81%; MAC, n = 49, 90%) abnormal karyotypes. Conclusions: HCT for children with RCMD showed better OS rate than that for AYA with RCMD. HCT using RIC regimen provided good outcomes for RCMD in children with or without abnormal karyotypes. Even in AYA, HCT using RIC regimen showed OS rate comparable to MAC regimen in both groups with and without abnormal karyotypes.

Unsupervised Clustering Analysis of Regimen and HLA Characteristics Identifies Subgroups with Improved Relapse-Free Survival in Children with ALL and AML Undergoing Umbilical Cord Blood Transplantation

Introduction. Umbilical cord blood transplantation (UCBT) is an efficacious therapeutic intervention for pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, contention persists regarding how best to achieve long-term relapse-free survival (RFS). Differences in clinical practice can be attributed to an incompletely understood interplay between graft-versus-leukemia (GvL) effect and graft-versus-host disease (GvHD), as well as an incomplete understanding of how UCBTs differ from those of other stem cell sources. Human leukocyte antigen (HLA) matching is a critical determinant of post-transplant outcome, but factors such as GvHD prophylaxis and total body irradiation (TBI) usage also play a key role. Objective. To use unsupervised clustering algorithms to examine the interplay between HLA matching, immunosuppressive regimens, and conditioning factors with greater power than that conferred by conventional multivariate regression analyses. Methodology. Data pertaining to UCBTs performed for pediatric ALL (n = 908) and AML (n = 417) between 2004 and 2022 was obtained from the Eurocord/EBMT registry. ALL and AML UCBTs were separately subjected to a partitioning around medoids clustering algorithm, which identified k = 15 ALL clusters and k = 11 AML clusters. These clusters were used to form hypotheses for post-hoc testing, which were tested using Kaplan-Meier and competing risks analyses. Results. Clusters of both diseases were frequently divided by usage of ATG, which was administered in 77% of 8/8 ABCDR matched UCBTs. ALL and AML patients who did not receive ATG experienced greater RFS than recipients of ATG, and this appeared to be driven by elimination of relapse mortality in the late (≥5 year) post-transplant setting (Figs 1-2). ALL clusters were frequently divided by use of total body irradiation (TBI), and those featuring TBI regimens conferred RFS comparable or superior to non-TBI regimens; this appeared to be driven by a reduction in relapse mortality within the first three years post-UCBT (P = 0.007). In AML but not ALL, both HLA-C and KIR match levels appeared to be relevant (P = 0.04), despite typing only having been performed for 70% and 24% of AML UCBTs, respectively. Patients receiving a 7/8 ABCDR-matched graft with a single HLA-C mismatch experienced significantly poorer RFS than 8/8 matched UCBTs (P = 0.04), but a concomitant single co-mismatch at HLA-A or HLA-B appeared to restore RFS to levels comparable to 8/8 matched grafts. Conclusions. ATG is over-used in ALL and AML patient-graft pairings where risk of non-relapse mortality (NRM) is low, and this may be creating an avoidable risk of relapse. The conflicting results in published literature may be explained by follow-up time, as the effect does not become apparent until 5 years post-UCBT and many studies do not follow patients beyond this. Incorporation of TBI into ALL myeloablative regimens prevents relapse mortality in the early to mid-post UCBT setting, and this effect was independent of HLA matching. These findings align with the known genetic and biological determinants of these diseases and redouble the importance of typing at HLA-C in AML; administration of TBI in ALL; and a measured approach to the usage of ATG.

Clinical Determinants of Early Mortality Following Allotransplantation for Acute Lymphoblastic Leukemia in a Brazilian Multicenter Registry

Introduction: Allogeneic stem-cell transplantation (HSCT) continues to be a potentially curative approach for acute lymphoblastic leukemia (ALL). However, one of the primary challenges in HSCT remains the transplantation-related mortality (TRM), even though the overall complications and mortality rates have decreased over time. Notably, in developing countries, previous research on HSCT has highlighted that early mortality plays a significant role in their comparatively worse outcomes. Therefore, it is crucial to identify the factors involved in early mortality to enhance cure rates. Considering this, our study aims to investigate the risk factors associated with early mortality following HSCT for ALL in Brazilian centers. Methods: This is a retrospective registry study. Patients with ALL or ambiguous lineage leukemia above 16 years who underwent a first HSCT in 5 Brazilian centers between January 2007 and December 2017 were included. Early mortality (EM) was defined as death within 100 days from HSCT. A multivariable analysis (MVA) was performed using logistic regression, with the Akaike's information criteria used for model selection. A p-value&amp;lt;0.05 was considered statistically significant. Results: Overall, 275 patients were included in this study. Baseline characteristics are summarized in Table 1. The median age was 31y (range, 16-65) and 58.5% were male. The Philadelphia chromosome was reported in 35% and most patients were in first complete remission (CR1) (66%). Matched sibling donor (MSD), matched unrelated donor (MUD), mismatched unrelated donor (MMUD), haploidentical donor, and umbilical cord were reported in 53%, 19%, 9%, 19%, and 5%, respectively. The median donor age was 31y (range, 4-64) and 54.4% were male. EM rate was 24.4%. Univariate analysis pointed some factors statistically related to EM, as it follows: graft source (p&amp;lt;0.001), baseline KPS (p=0.03), gender (female vs. male, 16.7 vs 27.9%, p=0.03), Ph-positive status (p=0.03), refractory disease status (p=0.015), umbilical cord blood source (p=0.01), and donor age (p=0.08). There was no difference regarding EM rates between public and private centers (24.5 vs. 19%, p=0.463). The best multivariable model included gender, Ph-status, donor type and donor age as final variables for EM. In our cohort, Ph-positive status (OR = 2.83), donor age (OR = 1.05), and the use of MUD (OR = 3.68) were independently associated with early transplant-related mortality. Regarding the cause of EM, 69% were related to infection, and 19.5% were caused by acute GVHD. Interestingly, EM was higher in Ph-positive patients with no major molecular remission (BCR-ABL≥0.1%) - 40 vs. 3.6%, p=0.008). Cumulative incidence of acute GVHD at day 100 was 48.3% by competitive analysis. Only 3 out of 62 deaths in EM group were due to disease relapse. Remaining deaths were secondary to bacterial infection (52%), followed by acute GVHD (17.8%) and fungal infection (8.9%), mainly. Conclusions: This study represents the largest analysis in Brazil to assess early transplant-related mortality in ALL patients. Reducing EM rates is particularly important in resource-constrained settings to improve outcomes. While the overall patient characteristics were similar to other registry analyses, the EM rate in this study was higher than that reported in other cohorts worldwide. Notably, transplant-related factors such as donor age and type, in addition to Ph-positive status, were found to be associated with EM, outweighing previously known factors like conditioning intensity and the use of total body irradiation. These findings could aid in enhancing donor selection in Brazil and optimizing HSCT indications in specific subsets.

Incidence and outcomes of subsequent malignancy after allogeneic hematopoietic stem cell transplantation in adult patients with severe aplastic anemia

The allogeneic hematopoietic stem cell transplantation (HSCT) is widely performed for the curative treatment of severe aplastic anemia (SAA). After HSCT, the long-term survival rates of SAA patients have substantially improved, with reported over 80%. However, as the post-HSCT survival period extends, there is a risk of exposure to long-term complications associated with HSCT. One such complication is the development of subsequent malignancies (SNs), which has observed to occur 2-5 times more frequently in HSCT recipients compared to age-matched controls. Although SN can have a critical impact on the survival of patients with SAA post-HSCT, there has been a lack of large-scale, long-term observational studies on the occurrence of SNs after HSCT in a disease of SAA. In this background, we investigated the incidence of SNs after HSCT in adult patients with SAA. This study is a single-center retrospective cohort study conducted on adult patients with SAA who received HSCT from 2002 to 2021. We analyzed the frequency of SN that occurred after HSCT, and the SN types were denominated according to the Surveillance, Epidemiology, and End Results (SEER) database classification. In addition, the cumulative incidence of SNs were analyzed considering death as a competing risk, and the risk factors influencing the occurrence of SN after HSCT were examined using the Fine-Gray model. Total 376 patients were included, and their median age at the time of HSCT was 35 (interquartile range, IQR: 27-46). Of them, 52.9% had received immunosuppressive treatment (ATG+CsA or CsA) before HSCT. HLA-matched sibling, unrelated, haplo-identical donors compromised of 48.7%, 31.6%, and 19.7%, respectively. During the observation period, 30 cases (7.2%) of SN were observed. one patient diagnosed with primary malignancies three times, and another patient having two primary malignancies. Among subsequent malignancies, 33.3% were hematologic malignancies, and 66.7% were solid malignancies. The frequencies of hematologic malignancies were as follows: Post-transplant lymphoproliferative disorder (23.3%), myelodysplastic neoplasm (6.7%), and acute myeloid leukemia (3.3%). The most common solid malignancies were thyroid cancer (26.7%), followed by stomach cancer (13.3%), oral cavity &amp; pharyngeal cancer (10.0%), esophageal cancer (6.7%), bladder cancer, skin cancer, and cervical cancer (3.3% of each). The 15-year cumulative incidence of all malignancies was 13.4% (95% confidence interval [CI]: 7.3%-23.9%) (Figure A). After SN diagnosis, the overall survival rate from the diagnosis of SN (n=27) was 72.3% (95% CI: 55.0%-95.2%) at 12 years (Figure B). The 15-year post-HSCT survival rate for SN patients from the date of HSCT was 74.6% (95% CI: 85.6%-94.9%), which was significantly lower than the survival rate of patients who did not develop SN (n=334, 92.4% [95% CI: 89.6-95.2]) (Log-rank test p = 0.03). Factors identified to have significant impact to the occurrence of SN were the use of Total body irradiation (HR 7.58 [95% CI: 1.07-53.83]) and ATG usage of more than 5mg/kg (HR 7.97 [95% CI: 1.22-52.23]) during HSCT (Table A). We observed occurrences of SN in a considerable proportion of SAA patients after HSCT. Our finding highlights that SN adversely affects survival, and the use of TBI and high dose of ATG were found to be significantly associated with SN occurrence. Therefore, SAA patients having these factors during conditioning regimen should be carefully monitored after HSCT.

Hematopoietic Stem Cell Transplantation for Fanconi Anemia: Outcome and Prognostic Factors for Survival and Subsequent Neoplasms

Introduction Fanconi anemia (FA) is an inherited disorder of impaired DNA repair, associated with progressive bone marrow failure (BMF), leukemia, and cancer predisposition. Hematopoietic cell transplantation (HCT) may be curative for FA associated BMF, and changes in HCT practice over the past decades may have impacted outcomes in FA patients. Methods We used CIBMTR database to perform a retrospective cohort study of children and adults undergoing first allogeneic HCT for FA BMF (patients with MDS/AML excluded) from 2000-2018. We hypothesized that contemporary HCT approaches, including decreases in radiation and increase in use of serotherapy and ex-vivo graft manipulation, would associate with improved outcomes in FA patients receiving HCT. The primary endpoints were overall survival (OS) and early subsequent malignant neoplasm (SMN; by 5 yr post-HCT). Secondary endpoints included event free survival (EFS; death, SMN or graft failure), treatment related mortality (TRM), graft failure, and acute (grade II-IV) and cGVHD. Univariate and multivariate Cox regression models were created to evaluate the impact of conditioning, donor and graft source, treatment era, and patient characteristics on outcomes, adjusting for other significant covariates. Due to confounding factors, we were not able to create a single multivariate model that included radiation, ex-vivo graft manipulation, and donor and graft source; therefore, we performed subgroup univariate analysis for patients receiving unrelated donor bone marrow (BM) or peripheral blood stem cell (PBSC) HCT. Results We analyzed 652 HCTs from 2000-07 (n=353) and 2008-18 (n=293). 223 (35%) patients had a matched related donor (MRD) with any graft type, 244 (38%) had an unrelated donor BM or PBSC grafts, 123 (19%) had an unrelated cord blood graft, and 44 (7%) had a related haploidentical donor with any graft type. Between the two treatment eras, 5-yr OS has dramatically improved (78.8% 2008-18 v 62.5% 2000-07, p&amp;lt;0.01; figure 1) driven by lower 5-yr TRM (15.2% v 25.5%, p=0.004) and lower rates of primary (7.9% v 12.9% at 42 days, p=0.038) and secondary (4.1% v 8.9% at 1 year, p=0.014) graft failure. No statistically significant change was observed for aGVHD, cGVHD, or early SMN. Assessing the entire cohort, use of total body irradiation (TBI) &amp;gt;300cGy was associated with lower OS (HR=1.75, 95% CI 1.24-2.47) and increased TRM (HR=3.36, 95% CI 1.54-7.34; figure 2) on multivariable analysis. For patients that received unrelated BM or PBSC HCT, use of TBI was associated with inferior OS survival (HR=1.93, 95% CI 1.18-3.17), EFS (HR=1.78, 95% CI 1.13-2.80), and TRM (HR=2.31, 95% CI 1.20-4.46) on univariate analysis. Among all patients, CD34 selection or T-cell depletion ( ex vivo depletion) were not associated with better OS (95% HR=1.014, 95% CI 0.84-1.56), EFS (HR=1.163, 95% CI 0.86-1.58), or TRM (HR=0.79, 95% CI 0.52-1.19) but was associated with less aGVHD (HR=0.35 95% CI 0.22-0.57) and lower but not-statistically significant cGVHD (HR=0.54, 95% CI 0.29-1.01) on multivariable analysis. Within the unrelated donor setting, univariate analysis showed reduced aGVHD (HR=0.39 95% CI 0.23-0.68) and cGVHD (HR=0.47 95% CI 0.28-0.79) but did not have a significant effect on OS, EFS, or TRM. Early SMN occurred in 3.2% of participants by 5-years post-HCT and was associated with cGVHD occurrence (HR=2.14, 95% CI 1.06-4.33) and older age (&amp;gt;18 v &amp;lt;9 years, HR=6.35, 95% CI 2.66-15.14), but not ex-vivo depletion or use of ATG or alemtuzumab. Early SMN risk was not impacted by the use of TBI (HR=1.60, 95% CI 0.77-3.34), but secondary analysis demonstrated a trend towards a relationship with doses &amp;gt;300 cGy (HR=2.24, 95% CI 0.99-5.08). Conclusions Outcomes for patients with FA BMF have improved significantly in more recent HCT eras, driven by reductions in TRM and graft failure risk. Although radiation doses &amp;gt;300cGy were associated with greater toxicity, doses of 100-300cGy were not associated with inferior outcomes in our cohort. Use of CD34 selection or T-cell depletion may reduce the risk of GVHD in transplant FA patients, but does not appear to impact 5-yr OS. Risk for early SMN development in FA patients receiving HCT associates with older age and cGVHD.

CNS Prophylaxis in Adult ALL Patients after Stem Cell Transplantation: An EBMT Survey on General Practice

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for acute lymphoblastic leukemia (ALL) resulting in long-term remission. Despite advances in therapy, disease progression remains the major cause of mortality following HSCT accounting for 20-50% of all deaths. The central nervous system (CNS) is the most common extra-medullary site of disease progression after transplant in ALL. The established practice of CNS prophylaxis for ALL has largely been modeled in the pediatric population, given the higher incidence of ALL in this age group compared with adults. Although the use of CNS prophylaxis as part of the upfront treatment for ALL has led to significant decreases in CNS relapse and improved outcomes overall, the routine use of post-HSCT prophylactic CNS therapy as a strategy to prevent CNS relapse after transplant in adult patients is still controversial. Studies that utilized post-HSCT CNS prophylaxis have reported disparate results and there is no generalized consensus regarding the use of post-transplant CNS prophylaxis to prevent relapse. Methods In order to assess the current practice of post-HSCT prophylactic CNS therapy in preventing CNS relapse in ALL patients, we carried out a survey among EBMT centres to describe intrathecal (i.t.) prophylaxis or irradiation in HSCT for ALL in both patients with or without CNS manifestations at any time of disease (first or second complete remission [CR1, CR2] and relapsed/refractory [R/R] ALL). EBMT centres were asked whether they usually give i.t. prophylaxis or cranial irradiation before and after HSCT, and which drugs they use. Results Of 410 invited centres, 55 (13%) replied to the survey. Tables 1 shows the number of centres which use i.t. prophylaxis or cranial irradiation. Most of the 55 centres used both pre-and post i.t. prophylaxis and triple prophylaxis (steroids, cytarabine [AraC] and methotrexate [MTX]) was the most frequently adopted. As expected in the pre-transplant phase, almost 70% of centres use i.t. chemotherapy irrespective of the phase of the disease or of the use of total body irradiation (TBI) as conditioning regimen. In the post-transplant phase, the rate of i.t prophylaxis varies according to disease phase, TBI use, and history of CNS involvement pre HSCT. In patients w/o history of CNS involvement in CR1, i.t. prophylaxis is given in 23.6% and 21.5% (with or w/o TBI use, respectively). Notably in CR2 pts, i.t. prophylaxis is given in 20% of cases if the conditioning regimen includes TBI, and in 74.5% of cases if TBI is not used; 32.7% and 46.9% R/R pts (with or without TBI use, respectively) are given i.t. prophylaxis. In the setting of patients with history of CNS involvement in CR1, i.t. prophylaxis is given in and 30.9% and 38.2% (with or without TBI use, respectively); in CR2 pts, i.t. prophylaxis is given in 38.9% of cases if the conditioning regimen does not include TBI, and in 29.1% of cases if TBI is used; 38.9% and 45.3% R/R pts (with or without TBI use, respectively) are given i.t. prophylaxis. Pre-transplant cranial irradiation is planned in less than 10% of centres in CR1 and CR2 patients without CNS involvement, irrespective of the use of TBI in the conditioning regimen, while it is used in 22.4% and 25% of patients with R/R disease with or without TBI use for transplant, respectively. In the setting of patients with CNS involvement, among those in CR1 and CR2, approximately 30% receive pre-transplant cranial irradiation irrespective of TBI use, while 32.7% and 34.6% of patients receive cranial irradiation (with or without TBI use, respectively). Its use after transplant is uncommon irrespective of disease status at treatment. Conclusions CR2 pts (without CNS involvement) seem to be at higher risk of CNS relapse if TBI is not included in the conditioning regimen. R/R pts are always considered at higher risk for CNS relapse if TBI is not included in the conditioning regimen. Cranial irradiation before treatment is used in almost 1 out of 3 pts with CNS involvement despite the use of TBI as the conditioning regimen, and 1 out 4 R/R pts without CNS involvement at transplant. The rate of cranial irradiation after transplant is extremely low, irrespective of diseases status, previous CNS involvement or TBI use. In conclusion, the use of i.t. prophylaxis after HSCT in patients with or without CNS involvement is variable among European transplant centres, also in the era of novel therapies for patients with ALL.

Allogeneic Hematopoietic Stem Cell Transplantation in Advanced Systemic Mastocytosis

Purpose Advanced systemic mastocytosis (AdvSM) is driven by the KIT D816V mutation in &amp;gt;90% of patients (pts.). Depending on subtype, median survival is between 1.5 and 4 years. Despite recent advances on responses and survival due to the availability of effective KIT inhibitors, allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment option. Data on optimal timing, conditioning regimens, and pre- as well as post-alloHSCT treatments for maintenance or relapse are however scarce. Current recommendations mainly refer to a retrospective analysis published almost 10 years ago (Ustun et al., JCO 32, 2014). With the advent of new therapies and improved transplant procedures, more recently collected data on alloHSCT in AdvSM are needed for actual assessment of optimal treatment strategies. Patients &amp; Methods This retrospective analysis identified 71 pts. with AdvSM who underwent alloHSCT at 20 German centers between 1999 and 2021. Data were collected via the 'German Stem Cell Transplantation Registry (DRST)' and the 'German Registry on Disorders of Eosinophils and Mast Cells (GREM)'. Additional baseline characteristics and response status prior to, during and post alloHSCT were provided by the participating centers. Results At time of alloHSCT, median age was 59 years (range 21-84); 55/71 (77%) pts. were male. Median time between diagnosis of AdvSM and alloHSCT was 1.2 years (range 0.1-16.7). Pts. were grouped into (i) aggressive systemic mastocytosis (ASM, n=6) and SM with an associated hematological neoplasm (SM-AHN, n=24), totaling 30/71 (42%) ASM/SM-AHN pts., (ii) SM with an associated acute myeloid leukemia (SM-AML; 28/71, 39%) and (iii) mast cell leukemia ± AHN (MCL±AHN; 13/71, 18%). The median follow-up time after alloHSCT was 1.4 years (range 0-20.4). PFS and OS were 52% (SD ± 6.1%) and 62% (SD ± 5.9%) at 1 year, and 39% (SD ± 6.3%) and 50% (SD ± 6.2%) at 3 years. Discrimination between the three cohorts allowed a three-tier risk stratification (median PFS, 4.5 vs. 0.7 vs. 0.3 years, P&amp;lt;0.001; median OS, 9.0 vs. 3.3 vs. 0.9 years, P=0.007, Figure 1). Overall non-relapse mortality rate was 30% (21/71) including infectious complications in 8/21 (38%), GvHD in 1/21 (5%), cardiotoxicity in 1/21 (5%) and ‘combinations/not further specified’ in 11/21 (52%) pts. The 100-day non-relapse mortality was 8% (6/71; ASM/SM-AHN, 0/30; SM-AML, 4/28, 14%; MCL±AHN, 2/13, 15%). OS was associated with response status of SM (17/41, 41%; median OS 4.6 vs. 1.1 years, P=0.029) or AHN (26/43, 60%, median OS not reached vs. 0.4 years, P=0.003) prior to alloHSCT ( Figure 2). Univariable analyses revealed absence of a KIT D816V mutation (HR 2.9 [1.2-6.5], P&amp;lt;0.001) and a complex karyotype (HR 4.2 [1.8-10.0], P=0.016) as adverse prognostic factors regarding OS. PFS was significantly impacted by diagnosis of MCL±AHN (HR 3.5 [1.7-7.5], P&amp;lt;0.001), absence of a KIT D816V mutation (HR 2.5 [1.2-5.4], presence of a complex karyotype (HR 4.2 [1.8-10.0], P=0.016), P=0.021) and absence of the use of tyrosine kinase inhibitors prior to alloHSCT (HR 0.461 [0.249-0.854], P=0.014). In contrast, HLA match (complete vs. incomplete), type of conditioning (myeloablative vs. dose-reduced intensity), use of total body irradiation (≥8 Gy yes vs. no) or the transplantation at high volume centers (≥7 patients yes vs. no) were not associated with significant differences in PFS or OS. During or after alloHSCT, 30/71 (42%) pts. showed either refractory (9/71, 13%) or relapsed (21/71, 29%) disease (R/R), being highest among MCL±AHN pts. (11/13, 85%; ASM/SM-AHN, 9/30, 30%; SM-AML, 10/28, 36%; P=0.002). R/R SM was predominantly observed in MCL±AHN (10/11, 91%) while R/R AHN was higher in SM-AML patients (6/10, 60%) and ASM/SM-AHN (5/9, 56%). The median time to relapse was 0.6 years (range 0.1-4.5). Post alloHSCT, a response to various treatment regimens was achieved in 13/30 (43%) pts. (ASM/SM-AHN, 3/9, 33%; SM-AML, 5/10, 50%; MCL±AHN, 5/11, 45%) with highest response rates in 9 pts. receiving midostaurin and/or avapritinib (7/9, 78%). Conclusions In pts. with AdvSM eligible for alloHSCT, i) baseline characteristics affect outcome of alloHSCT more than specific transplant procedures, ii) alloHSCT should not be performed in pts. without response prior to alloHSCT and iii) post-alloHSCT strategies such as preemptive or residual disease guided maintenance therapy should be considered to improve post-alloHSCT outcome.

TCRαβ/CD19 cell–depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis

AbstractTCRαβ/CD19 cell depletion is a promising graft manipulation technique frequently used in the context of human leukocyte antigen (HLA)–haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of exvivo T-cell depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median, 47.6 months for surviving patients). With a 5-year cumulative incidence of nonrelapse mortality of 5.2% (95% confidence interval [CI], 2.8%-8.8%) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9%-29.2%), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI, 68.6%-80.9%) and 71.6% (95% CI, 64.4%-77.6%), respectively. Cumulative incidence of both grade II-IV acute and chronic graft-versus-host disease were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including type of disease, use of total body irradiation in the conditioning regimen (hazard ratio [HR], 0.5; 95% CI, 0.26-0.98; P = .04), disease status at HSCT (complete remission [CR] ≥3 vs CR 1/2; HR, 2.23; 95% CI, 1.20-4.16; P = .01), and high levels of pre-HSCT minimal residual disease (HR, 2.09; 95% CI, 1.01-4.33; P = .04) were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable on those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.

Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Long-Term Adverse Events of Total Marrow Irradiation (TMI)-Based Conditioning Chemotherapy in Hematopoietic Stem Cell Transplant Recipients Treated on a Phase I/II Trial

Hematopoietic stem cell transplant (HSCT) remains a curative option for many hematologic malignancies. However, disease relapse is still one of the major causes of death after transplant. Increasing the intensity of conditioning regimens may elicit more antitumor activity but not without additional risk of transplant-related morbidity and mortality. The use of total body irradiation (TBI), while it can be effective, carries the risk of long-term toxicity to extramedullary organs, as well as secondary cancers. We have previously demonstrated that the combination of myeloablative chemotherapy with intensity-modulated radiation therapy to the bone marrow, or TMI, delivered with a linear accelerator, does not increase the toxicity of transplant in the first year of follow up (PMID 29065747; PMID 25234438). However, the effects of TMI in long term survivors after hematopoietic stem cell transplant (HSCT) has not yet been described. In this study, we retrospectively analyzed 24 consecutive patients who received HSCT with a TMI-based conditioning regimen between 2014 and 2021. The median age was 55.5 (range: 20-70) years. The median post-transplant follow up was 37.8 (range 12.0-89.7) months. Of 24 patients, 9 were diagnosed with multiple myeloma (MM) and received an autologous HSCT conditioned with high-dose Melphalan combined with either 3 (n=3), 6 (n=1) or 9 (n=5) Gy TMI. 15 (10 with acute myeloid leukemia, 3 with myelodysplastic syndrome and 2 with chronic myeloid leukemia) received an allogeneic HSCT from either a matched or 1-antigen mismatched related or unrelated donor, combining TMI 9 Gy with myeloablative fludarabine-IV busulfan. We then analyzed the incidence adverse events reported in published studies of TBI-based HSCT in our patient population (Table 1). In our long-term HSCT survivors receiving TMI-based conditioning, we observed xerostomia in 9 cases (37%, 3 of which had eating impairment), osteopenia or osteoporosis in 8 (33%, 2 of which also had fractures), dental in 29% and cataracts in 29%. Three subjects developed chronic kidney disease (12.5%, 2 patients developed stage 3 and 1 developed stage 4), 2 developed hypothyroidism (8%) and 2 patients developed heart failure (8%, both with mild decrease in ejection fraction without clinical decompensation). Only one patient (4%) developed a secondary malignancy (T-large granular lymphocytic leukemia). One patient (4%) developed a chronic interstitial pneumonitis, which was of unclear etiology and resolved spontaneously, but severe enough to require oxygen. These rates were overall lower than those historically reported with TBI (PMID 29482775) and can also be attributed to the standard chemotherapy utilized in the conditioning regimens. In conclusion, TMI is a relatively safe treatment modality when included in myeloablative conditioning regimens for HSCT. The adverse events profile in our patient population was similar to that of TBI but with lower incidence rates for the majority of reported events. Phase 2 clinical trials using TMI in conditioning regimens are currently underway to assess HSCT outcomes and should guide its future use in HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Non-Hodgkin Lymphoma: Secondary Analysis from Two Multi-Center Randomized Controlled Trials of Hematopoietic Cell Transplant Survivorship Interventions

Background: Autologous hematopoietic cell transplantation (AHCT) recipients with Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL) who survive progression-free for ≥2years can expect a 5-year overall survival rate of 90% (Myers et al, Cancer, 2018). However, patient-reported outcomes (PROs) in long-term lymphoma survivors after AHCT have not been well described. We present secondary analyses from a combined baseline dataset from two multi-center randomized clinical trials of HCT survivorship interventions, enrolling at 18 US transplant centers, including a large cohort of 1-10-year lymphoma AHCT survivors. Our objectives were to describe health-related quality of life (HRQoL) and cancer and treatment-related distress (CTXD), and to examine their associations with available clinical and sociodemographic correlates. Methods: Cross-sectional data at the time of study enrollment were pooled from two trials: SCP (Survivorship Care Plan; NCT02200133) and INSPIRE (INternet Survivorship Program with Information and REsources; NCT01602211). The SCP study enrolled patients (N=456) who were in a stable remission 1-5 years after transplant and the INSPIRE study enrolled survivors (N=1177) who were 2-10 years post-transplant, between 2003-2014. This analysis was restricted to AHCT recipients with diagnosis of HL or NHL. Our objectives were to describe HRQoL and cancer related distress (CTXD), and to examine their association with available baseline correlates. HRQoL was assessed using SF-12 v2 (12-item short survey form) and described as physical component summary (PCS) and mental component summary (MCS) T-scores (higher scores indicated better functioning). Comparisons between SF-12 scores and age-matched population norm (mean score 50, standard deviation [SD] 10) were analyzed using paired t-tests. Distress was assessed using the CTXD instrument, which reports mean scores from 0 to 3, with higher scores indicating greater distress. Based on prior receiver operating characteristic analysis, CTXD score >1.1 was considered clinically significant. Multivariate linear regression models were performed to evaluate the association of PCS score, MCS score, and CTXD with the following variables: diagnosis (HL vs. NHL), sex, race/ethnicity, number of HCT, use of total body irradiation (TBI) for AHCT, subsequent allogeneic transplant, age at time of enrollment, and time since AHCT. Results: Of 522 HL and NHL AHCT recipients, 60% were male, 94% were Caucasian, 94 (18%) had HL, 428 (82%) had NHL; 26 (5%) received >1 HCT, including 16 (4%) who received a subsequent allogeneic HCT. 8% patients received TBI-based conditioning regimens. Median age at index AHCT was 55 (range: 17-80) years, and median time from AHCT to study entry was 5 (range: 2-11) years. The mean [±SD] PCS T-score in the study population (48.96 [±10.59]) was slightly lower than the population norm (50 [±10]) (p=0.03). Mean [±SD] MCS T-scores were not significantly different between patients (50.75 [±10.40]) and general population (50 [±10]) (p=0.16) (Figure 1). The mean CTXD score was 0.79 (±0.59), with 135 (26%) patients reporting clinically significant distress (mean score ≥ 1.1). Among CTXD domains, "health burden” and "uncertainty” accounted for the highest burden of clinically significant distress, with 42% and 35% of patients reporting distress in these domains, respectively (Figure 2). On multivariable analysis, older age at study entry was associated with higher MCS score (estimated slope: 1.3 [95% CI: 0.5-2.2]; p=0.002), although there was no association of age with PCS score or CTXD. We did not observe associations of other variables and PCS score, MCS score, or CTXD. Conclusions: Patients with HL and NHL who are long-term disease-free survivors of AHCT have lower physical HRQoL compared to general population, although the difference is not clinically meaningful. Mental HRQoL in HL and NHL AHCT survivors is similar to general population. Older age is associated with higher mental HRQoL. Approximately a quarter of patients report clinically significant cancer and treatment-related distress. Survivorship programs should continue to screen for, and address concerns regarding HRQoL and distress. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chronic conditions, late mortality, and health status after childhood AML: a Childhood Cancer Survivor Study report

AbstractFive-year survival following childhood acute myeloid leukemia (AML) has increased following improvements in treatment and supportive care. Long-term health outcomes are unknown. To address this, cumulative incidence of late mortality and grades 3 to 5 chronic health condition (CHC) were estimated among 5-year AML survivors diagnosed between 1970 and 1999. Survivors were compared by treatment group (hematopoietic cell transplantation [HCT], chemotherapy with cranial radiation [chemo + CRT], chemotherapy only [chemo-only]), and diagnosis decade. Self-reported health status was compared across treatments, diagnosis decade, and with siblings. Among 856 survivors (median diagnosis age, 7.1 years; median age at last follow-up, 29.4 years), 20-year late mortality cumulative incidence was highest after HCT (13.9%; 95% confidence interval [CI], 10.0%-17.8%; chemo + CRT, 7.6%; 95% CI, 2.2%-13.1%; chemo-only, 5.1%; 95% CI, 2.8%-7.4%). Cumulative incidence of mortality for HCT survivors diagnosed in the 1990s (8.5%; 95% CI, 4.1%-12.8%) was lower vs those diagnosed in the 1970s (38.9%; 95% CI, 16.4%-61.4%). Most survivors did not experience any grade 3 to 5 CHC after 20 years (HCT, 45.8%; chemo + CRT, 23.7%; chemo-only, 27.0%). Furthermore, a temporal reduction in CHC cumulative incidence was seen after HCT (1970s, 76.1%; 1990s, 38.3%; P = .02), mirroring reduced use of total body irradiation. Self-reported health status was good to excellent for 88.2% of survivors; however, this was lower than that for siblings (94.8%; P < .0001). Although HCT is associated with greater long-term morbidity and mortality than chemotherapy-based treatment, gaps have narrowed, and all treatment groups report favorable health status.

Feasibility study of volumetric modulated arc therapy with Halcyon\u2122 linac for total body irradiation

BackgroundThe use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI.MethodsVMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes.ResultsThe PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1–2 h. Dose calculation and optimization was performed for 3–4 h. Quality assurance (QA) took 2–3 h. The treatment duration was 23 min.ConclusionsA planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.

Review of Unrelated Donor Cord Blood Transplantation in Children over the Past 3 Decades

Review of Unrelated Donor Cord Blood Transplantation in Children over the Past 3 Decades

Trends in Late Mortality and Life Expectancy after Autologous Blood or Marrow Transplantation (BMT) Performed over Three Decades - a BMT Survivor Study (BMTSS) Report

Background: Advances in therapeutic and supportive care strategies have led to increasing use of autologous BMT to ensure durable disease-free survival in patients with hematologic malignancies. However, autologous BMT recipients carry a high burden of morbidity. The cumulative effect of autologous BMT and the long-term morbidity on life expectancy remains unknown. Further, the impact of changes in transplant practice (older age at BMT, increasing proportion of patients undergoing autologous BMT for plasma cell dyscrasias [PCD], increasing use of peripheral blood stem cells [PBSCs] and decreasing use of total body irradiation [TBI]) on late mortality and life expectancy remains unknown. We determined trends in life expectancy and cause-specific late mortality after autologous BMT performed over a 33y period (1981-2014) using the resources offered by BMTSS - a multi-institutional collaborative designed to examine late morbidity and mortality after BMT.Methods: This retrospective cohort included 4,702 individuals who lived ≥2y after autologous BMT performed between 1981 and 2014 at three transplant centers. We examined trends in life expectancy and late mortality over four eras: 1981-1999; 2000-2005; 2006-2010; 2011-2014. Endpoints included all-cause, recurrence-related mortality (RRM) and non-recurrence-related mortality (NRM) and projected reduction in life expectancy. Information on vital status and cause of death was obtained from National Death Index (NDI) Plus program and Accurinct databases. End of follow-up was 04/19/2021.Results: Median age at BMT was 53y (range, 0-78); 58.7% were male, 67.8% non-Hispanic white. Median follow up after BMT was 9y (range, 2-36). PCD was the most common indication for autologous BMT (42.3%). PBSCs were used for 91.6% of the transplants and TBI was used for conditioning in 23.1% of the patients. Across the four eras, the median age at BMT increased (40y→58y), as did the proportion of patients receiving autologous BMT for PCD (13.7%→60.0%) and the proportion of patients receiving PBSCs as the stem cell source (66.6%→99.5%). There was a dramatic decline in the proportion of patients conditioned with TBI (56.4%→5.2%), and those transplanted for acute myeloid leukemia/ myelodysplastic syndrome (AML/MDS) (15.4%→0.2%). Conditional on surviving ≥2y after autologous BMT, patients experienced a 25.8% reduction in life expectancy, representing 7.0y of life lost. In an analysis adjusted for all relevant demographic and clinical predictors and restricted to 5y of follow-up, the years of life lost declined across the four eras from 5y to 1.6y (Fig 1) The adjusted hazard of all-cause mortality also declined over the four eras (reference: 1981-1999; hazard ratio [HR]2000-2005=0.77; 95%CI=0.7-0.9; HR 2006-2010=0.62; 95%CI=0.5-0.7; HR 2011-2014=0.5; 95%CI=0.4-0.6; P trend <0.0001) (Fig 2). Mediation analysis revealed that the reduction in late mortality was evident among those transplanted for Hodgkin lymphoma (HL) or PCD, and among those who did not receive TBI . The 30y cumulative incidence of NRM (29.2%) was higher than that RRM (23.8%) (Fig 3). The adjusted hazard of RRM declined over the four eras (reference: 1981-1999; HR 2011-2014=0.55; 95%CI=0.4-0.7, P trend: <0.0001). Cause-specific late mortality declined for mortality related to infection (P trend <0.0001), subsequent malignant neoplasms (P trend=0.01), cardiovascular disease (P trend=0.001), and renal disease (P trend=0.0002), but not for pulmonary disease (P trend=0.3).Conclusions and Relevance: Late mortality among autologous BMT recipients has declined over a 30y period, likely due to changes in transplant practice (reduction in use of TBI) and improvement in disease-specific therapeutic strategies (newer therapeutic options for PCD and reduction in dose/volume of radiation for HL). Continued efforts need to focus on mitigation strategies for disease recurrence, subsequent neoplasms, infections, and cardiovascular, renal and pulmonary disease in this population. [Display omitted] DisclosuresArora: Kadmom: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding. Forman: Allogene: Consultancy; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company. Weisdorf: Incyte: Research Funding; Fate Therapeutics: Research Funding.

Outcomes of patients diagnosed with chronic lymphocytic leukemia after allogeneic hematopoietic stem cell transplantation: Results from a tertiary care center

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only curative treatment for patients with chronic lymphocytic leukemia (CLL). MethodsWe analyzed the outcomes of 93 patients (median age: 52 years) who underwent allo-HCT at our center between 1989 and 2019. ResultsAfter a median follow-up of 35 months, relapse was observed in 15.1% (n = 14) patients. The estimated 2-year non-relapse mortality, relapse-free survival, and overall survival (OS) were 38.1%, 54.2%, and 58.7%, respectively. The ECOG performance status ≥ 2 (hazard ratio [HR]: 4.1; p = .001) and use of total body irradiation (in a myeloablative conditioning regimen; HR: 2.64; p = .005) were predictive of poor OS after multivariable analysis. The occurrence of sinusoidal obstruction syndrome/veno-occlusive disease post-transplant was associated with poor survival (p = .001). ConclusionAlthough the use of kinase and bcl2 inhibitors may result in a decrease in the number and need of transplants, allo-HCT remains a viable option in selected patients with high-risk CLL and good performance status.

Oral mucositis in paediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation preventively treated with professional dental care and photobiomodulation: Incidence and risk factors.

Oral mucositis (OM) is an important side effect related to allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it has been associated with a significative reduction of quality of life. A negative impact of OM in paediatric patients could result in increased use of parenteral feeding and opioids, longer periods of hospitalization, and a higher risk of systemic infection. To investigate the clinical features and clinical outcomes associated with OM development and severity in hematological cancer paediatric patients undergoing allo-HSCT who underwent professional dental care (PDC) and photobiomodulation (PBM) as prophylactic treatment. Medical data and OM presentation were retrieved retrospectively from all patients younger than 18years who received allo-HSCT between 2013 and 2016. The incidence of OM was assessed and graded by two oral medicine specialists following the WHO guidelines, and it was correlated with clinical parameters. Forty-nine consecutive paediatric patients were included. OM was diagnosed in 73.5% of patients, and in 36.1% of patients, OM was classified as severe. Acute lymphoblastic leukemia as a primary diagnosis and the use of a myeloablative regimen were associated with OM development. The primary diagnosis and use of total body irradiation (TBI) were associated with aggressive OM. Neither the incidence nor the severity of OM affected the overall survival, whereas only the use of a myeloablative regimen and a high body mass index (BMI) were determinants of lower OM-free survival rates. A myeloablative conditioning and a high BMI were observed to be independent prognostic determinants of a lower OMFS rate. The cluster analysis allowed us to outline patient profiles with greater susceptibility to the development and severity of oral mucositis, which seems to be a useful tool to determine the risk of OM in paediatric patients.