Patients Undergoing Stem Cell Transplantation Research Articles

Treatment challenges and outcomes of older patients with acute myeloid leukemia from India.

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

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.

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).

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.

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.

Recirculating Regulatory T Cells Mediate Thymic Regeneration in a ZFP36L1 and Amphiregulin Dependent Manner

T cell reconstitution correlates with outcomes in patients undergoing stem cell transplantation (HCT). A functional thymus is needed for the maturation of T cells, but unfortunately, the thymus is highly sensitive to acute injury, such as cytoreductive conditioning given to HCT patients. To enhance T cell reconstitution, it is therefore imperative to explore therapies that can boost thymic regeneration and T cell output. Regulatory T cells (Tregs) are known to mediate homeostasis and tissue regeneration in a variety of tissues, but their role in thymic injury is not known. This study aims to shed light on the role of regulatory T cells (Tregs) in thymic regeneration. Using a model of thymic injury and regeneration in mice receiving sublethal total body irradiation (SL-TBI, 550cGy), we observed a significant increase in Tregs ( Fig. 1A), located in both the medullary and cortical areas of the thymus on multiparameter immunohistochemistry. Employing a targeted ablation of Tregs at the time of injury using the FOXP3DTR mouse model, we could observe significant delay in thymic regeneration in mice depleted of Tregs (day 7 post SL-TBI, p=&amp;lt;0.0001, n=10, Fig. 1B). RAG2GFP mice, where GFP is expressed under the RAG2 promoter, have been used to discern recirculating and de-novo produced Tregs. To characterize the nature of the Treg expansion, we treated RAG2GFP mice with SL-TBI and analyzed their thymus at multiple time points after injury. Interestingly, the increase in Tregs was mainly due to recirculating RAG2-GFP- Tregs but not de-novo produced RAG2+GFP+ Tregs after injury. Brdu administration after injury indicated proliferation of these RAG2-GFP- Tregs. Parabiotic experiments linking RAG2GFP mice expressing either the congenic marker CD45.1 or CD45.2 confirmed the recirculating nature of these cells, both at steady state and after injury. Furthermore, when adoptively transferring sorted Thymic Tregs from FOXP3RFP mice to mice receiving SL-TBI, we significantly enhanced thymic cellularity after injury and homing of these Tregs to the thymus. To discern the transcriptional profile of these cells, we used single-cell sequencing of CD45+ RAG2- cells in 2- and 18-month-old RAG2GFP mice before and at day 1, 4, and 7 after sublethal irradiation. This enabled us to discover the age- and injury-associated changes in recirculating T cells. While the aged thymus had a similar surge of Treg numbers after injury, this response was blunted compared to their young counterparts. Factor normalization methods enabled us to find two distinct gene regulatory networks highly specific to the RAG2-GFP-Tregs. One gene network was highly enriched for Zfp36l1, a poised RNA known to mediate cell stability. Selectively ablating Zfp36l1 in Tregs using the Foxp3Cre ZFP36L1 flox/flox model impaired regeneration significantly after SL-TBI. The other distinct RAG2-GFP- Treg specific gene network was enriched for the regenerative factor Amphiregulin ( Areg). Amphiregulin was seen to be increased in thymic supernatants, and its receptor Egfr was seen to be transcriptionally upregulated in thymic epithelial cells after injury. In parallel, the most significantly upregulated pathway using cell-to-cell interaction prediction models on single-cell data indicated a strong likelihood of Treg to thymic epithelial cell interactions through amphiregulin to Egfr. Functional inhibition of amphiregulin with an antibody enabled us to observe delayed thymic regeneration, indicating amphiregulin as a factor in the regenerative capacity of thymic recirculating Tregs. Mapping human gene orthologs of the gene regulatory program provided by factor normalization in murine RAG2GFP- Tregs on single cell data of human pediatric thymic samples from children undergoing open heart surgeries enabled us to distinguish a putatively analogous human population of recirculating thymic Tregs. This population was found to be amphiregulin positive. And human thymic epithelial cell cultures with recombinant amphiregulin enhanced the growth of human thymic epithelial cells, as measured by life imaging, and promoted signalling through MAPK ERK1/2. Taken together, our findings reveal a novel role for injury-resistant recirculating thymic regulatory T cells existing in both the human and murine thymus and may enable the development of new therapeutic targets for thymic regeneration for patients undergoing cytoreductive therapies.

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.

S950 A Mixed-Methods Analysis of the Insurance Experiences of Patients Undergoing Stem Cell Transplantation for Severe Crohn’s Disease

S950 A Mixed-Methods Analysis of the Insurance Experiences of Patients Undergoing Stem Cell Transplantation for Severe Crohn’s Disease

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day+7 and+30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an L:R ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. L:R ratios were increased at day+7 but returned to baseline at day+30 in most patients (P= .014). Conditioning regimen intensity did not affect the trajectory of L:R (P= .39). Baseline L:R ratios did not vary with diagnosis. L:R correlated with LBP levels (r2= 0.208; P= .0014). High L:R ratios were associated with lower microbiome diversity (P= .035), loss of anaerobic organisms (P= .020), and higher plasma LBP (P= .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through L:R ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.

Preservation of Peripheral Blood Stem Cells (CD34+/CD38-) for Bone Marrow Transplantation in Thai Lymphoma Patients

Abstract Hematopoietic stem cell transplantation (HSCT) is one method of lymphoma therapy. Peripheral blood stem cell (PBSC) separation, preservation, cell viability, and cell function before transplantation are important factors in the success rate of stem cell transplantation. This study aims to separate and estimate the efficiency of deep-freezing preservation in autologous PBSCs (CD34+/CD38-) from lymphoma patients undergoing stem cell transplantation. PBSCs were separated and collected by leukapheresis before being cryopreserved and stored in liquid nitrogen. The number of CD34+/CD45dim cells was investigated and compared with the subpopulation of CD34+/CD38- cells using conventional trypan blue exclusion method and 7-AAD before and after cryopreservation. Colony-forming units (CFUs) were determined to indirectly assess the viability and potency of the PBSCs. The result showed that CD34+/CD38– cells constituted 35.56% of total CD34+ cells and 0.05% of total nucleated cells (TNCs). After thawing, the number of CD34+/CD38- cells did not demonstrate significant differences compared with pre-storage. The percentage of CFU recovery was 94.74%. In this study, the storage process of deep-freezing cryopreservation demonstrated high-quality recovery of CD34+/CD38- cells from PBSCs for autologous hematopoietic stem cell transplantation in lymphoma patients. This result showed novel data about the preservation of CD34+/CD38- cells. Keywords: Lymphoma, Autologous peripheral blood stem cell, Blood cryopreservation, Bone marrow transplantation

Optimized vitamin D repletion with oral thin film cholecalciferol in patients undergoing stem cell transplant

AbstractVitamin D deficiency is common in childhood, pervasive before and after bone marrow transplant, and is associated with increased incidence of graft-versus-host disease (GVHD) and decreased survival in patients undergoing hematopoietic stem cell transplant (HSCT). Numerous barriers impede replacement, including malabsorption secondary to gut GVHD, mucositis, inability to take capsules, kidney disease, liver disease, and infection; many patients remain refractory despite vitamin D therapy. We hypothesized that a different formulation of cholecalciferol, administered on the tongue as a readily dissolving oral thin film (OTF), would ease administration and facilitate therapeutic vitamin D levels (>35 ng/mL) in patients who are refractory. In this prospective pilot study, we evaluated 20 patients after HSCT (range, day +21 - day +428 at enrollment) with serum vitamin D levels ≤35 ng/mL. Cholecalciferol OTF strips were administered for 12 weeks. Dosing was based on patient body weight and titrated per individual pharmacokinetics. Wilcoxon matched-pairs signed-rank test demonstrated marked improvement in all 20 patients who were formerly refractory, increasing from a median baseline vitamin D level of 29.2 ng/mL to 58 ng/mL at end of study (P < .0001). All patients demonstrated improvement in serum vitamin D level by week 4 on study, some of whom had been refractory for years prior. Median dose was 1 OTF strip (40 000 IU) per week. No toxicity was observed. This formulation proved to be safe, effective, efficient, and well received. We are eager to explore other patient populations, which might benefit from this promising development, and other therapeutics that might be optimized using this mode of delivery. This trial was registered at www.clinicaltrials.gov as #NCT04818957.

Delivering written peer support as a patient resource during hematopoietic stem cell transplant: Pros, cons, and clinician feedback on a new website.

e24215 Background: We developed a website that allows hematologic cancer patients undergoing stem cell transplant (SCT) to access a searchable, filterable database of peer support narratives—written first-hand accounts of SCT experiences and advice created by SCT survivors. The website, called Mosaic (Mosaico in Spanish), pairs the narratives with resources informed by patients, clinicians, and behavioral scientists including psychoeducation, support for patient-provider communication, and stress management and coping resources. This presentation will describe feedback about Mosaic from interviews with SCT clinicians and discuss pros and cons of delivering peer support in written form. Methods: We conducted semi-structured interviews with 13 SCT clinicians (3 oncologists, 3 nurse practitioners, 3 social workers, 3 registered nurses, 1 physician assistant; 92% women; 53.8% white). After describing Mosaic’s content and features, we asked for feedback on Mosaic’s potential benefits, harms, and recommended changes. Interviews were audio recorded, transcribed, and content analyzed by trained coders. Results: All clinicians noted potential benefits of Mosaic. Some focused on novel informational benefits (e.g., getting “the real patient experience,” giving patients “a sense of less isolation”). Others liked that Mosaic could help patients develop reasonable expectations of SCT, including things that can go wrong. A few clinicians liked features designed to meet patients’ differing needs (e.g., “they can filter out what they [don’t] want”). Overall, there was enthusiasm for Mosaic as a patient resource. Yet, all clinicians also mentioned at least one concern. Several wanted to see Mosaic’s full content before recommending it to patients. Others wanted evidence showing Mosaic’s benefits. A more frequent concern about misinformation suggested the need to edit narratives to remove medical advice and identifiable information. Some clinicians were concerned that patients might inappropriately worry about medical risks and complications described in narratives, although others felt that Mosaic’s disclaimers and other features mitigated this concern. Some recommendations for Mosaic addressed this concern (e.g., clearly disclosing that “it’s not medical advice” and that their SCT “experience may be completely different”). Other recommendations included a need for disclosures to help patients make an informed decision about using Mosaic and the need to monitor for adverse events such as distress. A recommended new feature included grouping narratives by year of SCT due to changing treatments. Conclusions: SCT clinicians felt Mosaic could provide important emotional and informational benefits. Their concerns and recommendations will be used to refine Mosaic to optimize safety and potential benefits in preparation for a clinical efficacy trial.

0306 Circadian Disrupting Light Exposure within Pediatric Hospital Rooms

Abstract Introduction Pediatric patients undergoing stem cell transplant (SCT) often experience extended hospitalizations. Inappropriate lighting during admissions is known to disrupt sleep and circadian health, which can result in worse health outcomes. This study aimed to describe patterns of light across 24-hour periods in two inpatient rooms of children undergoing SCT. Methods Wall-mounted light meters (Extech SDL400) continuously tracked noise and light levels at one-minute intervals in two patient rooms over six months. We determined the percent of time that patients were exposed to non-optimal light levels (&amp;lt; 448 lux during the daytime, &amp;gt;18 lux in the evening, &amp;gt;2 lux at night); thresholds were based on converting recent consensus-based melanopic equivalent daylight illuminance guidelines to vertically measured illuminance thresholds. We assessed the frequency that light exceeded thresholds associated with night wakings (&amp;gt;150 lux). Wilcoxon rank-sum tests compared light levels between the two rooms. Room A had a single northwest-facing window overlooking a narrow courtyard. Room B had an unobstructed window facing north. Results On average, hospitalized pediatric SCT patients spent 50% of their time in inappropriate light conditions. They were exposed to light spikes &amp;gt;150 lux on 2% of nights, with overnight light peaking at 513 lux. When comparing average daytime and nighttime light levels between the two rooms, Room A was significantly dimmer than Room B, p &amp;lt;.001. In the dimmer room, light levels never reached the recommended threshold during the daytime, and the light was too bright for 19% of the evening and 17% of the nighttime. In the brighter room, light levels were too dim during 97% of the daytime and too bright during 59% of the evening and 30% of the nighttime. Conclusion During the day, pediatric SCT patients are rarely exposed to light bright enough to preserve a healthy circadian rhythm. Hospitals have an opportunity to significantly improve the sleep and circadian health for children already at elevated risk for health morbidities during transplant. Support (if any) This research was generously supported by grant funding from Pedals for Pediatrics (PI: Zhou) and an institutional research training grant (T32DK063929).

Safe Regimen for Patients Undergoing Stem Cell Transplantation

Safe Regimen for Patients Undergoing Stem Cell Transplantation

Zanubrutinib, Alone and in Combination With Tislelizumab, for the Treatment of Richter Transformation of Chronic Lymphocytic Leukemia.

Zanubrutinib, Alone and in Combination With Tislelizumab, for the Treatment of Richter Transformation of Chronic Lymphocytic Leukemia.

Safety of Cryopreserved Stem Cell Infusion through a Peripherally Inserted Central Venous Catheter.

The management of patients undergoing stem cell transplantation requires a multipurpose central venous catheter (CVC) to facilitate drug administration, parenteral nutrition, transfusion of blood products, and collection of blood samples. Peripherally inserted central venous catheters (PICCs) appear to meet these requirements but are rarely used for stem cell infusion. We aimed to retrospectively assess the safety and feasibility of stem cell infusion through PICC and to evaluate its impact on transplantation kinetics. We retrospectively analyzed the outcomes of peripheral blood stem cell (PBSC) transplantation in patients receiving cryopreserved autologous or allogeneic PBSC by PICCs and compared the results with patients receiving transplants through a conventionally inserted central venous catheter (CICC). Despite statistically significant differences in CD34+ dose, infusion rate, and total length of administration, the clinical outcomes of transplantation, exemplified by platelet and neutrophil engraftment, along with the length of hospitalization, were not affected by the prolonged infusion time and lower infusion velocity in the PICC group. Our study showed that the clinical outcomes of PBSC transplantation did not differ between the PICC and CICC groups, suggesting that both types of catheters can be implemented in a PBSC transplantation setting.

Phase I Study of Ixazomib with Conventional Chemotherapy in the Treatment of Acute Myeloid Leukemia in Older Adults

Introduction: Outcome in acute myeloid leukemia (AML) for patients aged >60 years is poor with a median survival of approximately 11 months. Targeting the proteasome in AML is attractive, since leukemia stem cells demonstrate sensitivity to proteasome inhibition in preclinical models, perhaps through down regulation of nuclear NF-KB or MCL-1 through stabilizing effects on NOXA. AML cell lines are susceptible to synergistic cytotoxicity when bortezomib, a proteasome inhibitor, is combined with daunorubicin and cytarabine. We have shown that adding bortezomib to standard treatment in AML results in a high remission rate. A newer generation proteasome inhibitor, ixazomib, is less frequently associated with neurotoxicity, and, therefore, was selected for combination with conventional chemotherapy in this phase I trial. The primary objective of this study was to determine the recommended phase II dose (RP2D) of ixazomib in combination with intensive induction and consolidation chemotherapy for AML. A secondary objective was to determine if the level of CD74 in blasts correlated with response, since prior studies showed that CD74 may be a poor prognostic indicator, but its effect might be diminished with proteasome inhibition. Methods: Adults >60 years of age with newly diagnosed AML were screened for eligibility. Patients with secondary AML were eligible, including those with prior hypomethylating agent (HMA) therapy for myelodysplastic syndromes (MDS). We excluded those with promyelocytic leukemia. There were 2 phases in this study. In the first phase (A), the induction treatment consisted of the following: cytarabine 100 mg/m2/day by continuous IV infusion, Days 1-7; daunorubicin 60 mg/m2/day IV, Days 1, 2, 3, and ixazomib was provided orally at the cohort dose, Days 2, 5, 9, and 12. Consolidation or transplant in this phase was at the discretion of the treating physician. In the second phase (B), induction was administered with the established RP2D of ixazomib in phase A. All patients were to be treated with the following consolidation: cytarabine at 2 g/m2/day, days 1-5 with ixazomib on days 2, 5, 9, and 12 at the cohort dose for consolidation. A classical 3 + 3 patient cohort dose escalation design was used to determine whether the dose of ixazomib could be safely escalated in 3 cohorts (1.5 mg/day, 2.3 mg/day, 3.0 mg/day), initially in induction (phase A) and subsequently in consolidation (phase B). Secondary objectives included rate of complete remission (CR), disease-free survival (DFS), overall survival (OS), and outcome relationship with CD74. Results: Thirty-nine patients were enrolled, including 15 (38%) patients with secondary AML, either with antecedent myeloid malignancy or therapy-related AML. Twenty-six patients (67%) were male, and the median age was 68 years (range 61-80 years). There were no grade 5 toxicities attributed to study drug. Four patients died before day 30 with persistent leukemia, 3 of whom were replaced for assessment of the MTD. Three other patients were not evaluable and were replaced. Nearly all grade 3 and 4 toxicities were hematologic (Table). There was 1 DLT (grade 4 platelet count decrease extending beyond Day 42). There were no grade 3 or 4 neurotoxicity events attributable to ixazomib. Among the 38 patients evaluable for response, 26 achieved CR, and 2 achieved CR with incomplete count recovery (CRi), for a composite remission rate (CCR) of 74%. Among the 15 patients with secondary AML, 9 achieved CR and 2 achieved CRi, for a CCR of 73%. The median OS for the 39 patients is 40.8 months [95% CI, 17.6, Inf]. The 18-month OS estimate was 63% [95% CI, 49-80%]. Of note, 30 patients underwent stem cell transplantation. There was no significant association between level of CD74 expression on blasts at baseline and response. Conclusions: The highest dose level (3 mg) of ixazomib planned for induction and consolidation in this trial has been reached safely and is the recommended phase 2 dose for both. Notably, to date, no grade 3 or 4 neurotoxicity has been encountered. The remission rate for this regimen in this older adult population appears favorable. With ixazomib added in treatment, we saw no association of response rate with level of CD74 in blasts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

How Does Treatment Intolerance Affect Survival in Patients with Multiple Myeloma (MM)?

Background MM is the second most frequent hematological neoplastic disease. Management of MM is moving toward long-term continuous regimens , but this approach is sometimes difficult to implement due to multiple factors including intolerance to treatment. In this study, we aim to identify the factors associated with treatment intolerance and assess it impact on MM patient's outcome . Method We analyzed data from the Australian and New Zealand (ANZ) and Asia-Pacific (APAC) Myeloma and Related Diseases Registry (MRDR). Newly diagnosed MM patients that have stopped their treatment were included. The patients are further classified according to whether they stopped the treatment due to intolerances or other reasons. Categorical variables are compared using a chi-squared test, whilst for continuous variables a rank-sum test was used. Survival analyses we performed using the Kaplan-Meier method and statistical comparisons performed using a log-rank test. Results 4454 patients diagnosed MM in the registry. Of these, 2753 ceased treatment. 313 stopped due to intolerance, 2313 stopped due to other reasons and 127 were not classified and therefore excluded from the analysis. Compared to others, patients who stopped treatment due to intolerance were older (Median age 74.7 years vs 64.3 years, p<0.001), tended to have advanced disease (38.9% ISS3 vs 30.4%, p=0.009), had poorer performance status (33.6% ECOG2-4 vs 17.3% ECOG2-4), and more co-morbidities such as moderate to severe cardiac disease (16.8% vs 8.2%, p=0.001), pulmonary disease (7.7% vs 3.7%. p<0.001) and diabetes requiring treatment (18.8% vs 11.2%, p<0.001). Consistent with the patient profile, a lower proportion of the intolerant patients underwent stem cell transplantation and bortezomib based treatment whereas more patients in the intolerant group had lenamidomide based treatment. Importantly, there was no clinically relevant difference in duration of treatment between the intolerant and tolerant group, although there was a lower proportion patients achieving a partial response or deeper in the intolerant group (74% vs 88.8%, p<0.001) . On multivariate analysis, age was the predominant factor associated with intolerance, with the odds ratio increasing with age, whereas the use of velcade was relatively protective with an odds ratio of 0.33 (p<0.001). Patients who ceased treatment due to intolerance to treatment had shorter PFS (median PFS 36.8 months compared to 47.7 months, p<0.001) and OS (Median OS 47.5 months compared to 80.9 months, p<0.001). On multivariate analysis, intolerance to treatment itself was an independent prognostic factor. To remove the immortal time bias inherent in analyzing the effect of treatment duration on survival, we measured survival from the cessation of treatment. This analysis showed a shorter survival in the intolerant group (35.3 months compared to 68.4 months, p<0.001). When we added duration of treatment and depth of response to the multivariate model of survival, intolerance was no longer a significant prognostic factor, whereas depth of response was. Duration of treatment was also not significant [show table] Conclusion Intolerance to chemotherapy is associated with inferior survival, independent of potential confounding baseline variables associated with intolerance, in particular age and performance as well as chemotherapy regimen (ISS stage is not independently associated with an intolerant response once adjusted for age and performance status). The main reason for this appears to be reduced depth of response achieved. Optimizing treatment to achieve better tolerance and to increase chance of deeper response especially in the elderly, and those with comorbidities and poorer performance status, would be important in improving outcomes of MM patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Volumetric Modulated Arc Therapy Total Body Irradiation (VMAT-TBI) in Pediatric and Adolescent/Young Adult Patients Undergoing Stem Cell Transplantation: Early Outcomes and Toxicities

<h3>Purpose/Objective(s)</h3> Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy (VMAT-TBI). <h3>Materials/Methods</h3> We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019-2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse free survival (RFS) were analyzed using the Kaplan-Meier method. <h3>Results</h3> Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with non-myeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs D_mean was 7.3±0.3 Gy for myeloablative regimens (range: 6.8–7.8). Kidneys were spared to average mean dose of 71.4±4.8% of prescription dose. Gonadal sparing was achieved for patients treated for non-malignant diseases to D_mean of 0.7±0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. <h3>Conclusion</h3> VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

Psychosocial interventions with art and music during stem cell transplantation: An integrative review.

The objective of this study is to systematically review the literature with the following aims: to survey the art and music interventions offered to the stem cell transplant population; to define the interventions' beneficial properties by conceptualising themes; to analyse these themes using behavioural activation principles as a lens and explore their value in alleviating isolation-related distress. Patients undergoing stem cell transplant are at great risk of psychological morbidity, partly on account of prolonged hospital stays in protective isolation. This risk extends beyond discharge and into ambulatory care, negatively affecting quality-of-life and survival rates of the transplant recipients. Integrative review methodology. A systematic search of 10 bibliographic databases was undertaken using terms relating to art, music and stem cell transplantation for the years 2012 to 2019. Records were assessed for quality and risk-of-bias using a critical appraisal tool and following the PRISMA Systematic Review checklist to guide reporting. Studies were analysed narratively and thematically. The 16 papers were of mixed quality. Findings and treatment effects differed between and within studies. The beneficial attributes of the treatments were clustered and divided into two groups. The first consisted of intrinsic, patient-focussed factors: (1) Creative outlet or acquisition of a new skill; (2) achievement of normality; (3) mutual or peer-support; (4) relationship-building and (5) meaningful recreation, distraction and diversion. The second group considered extrinsic factors: (6) Improved communication; (7) enhanced spiritual care and (8) better healthcare experience. Several art and music interventions have been attempted which were beneficial to patients and generated a sense of achievement, connection and enjoyment. The interventions appear to uphold the principles of person-centred holistic care and have potential to generate a high-quality, supportive healthcare and working environment. Psychosocial interventions with art and music have improved the care and experience of patients undergoing stem cell transplant.