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BackgroundAllogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT.MethodsWe performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsOf the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence.ConclusionOur study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.

Aims: We studied melphalan pharmacokinetics (PK) and feasibility of melphalan full‐dose adjustment based on test‐dose PK in children and young adults with non‐malignant disorders (NMD) undergoing allogeneic hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) containing alemtuzumab, fludarabine and melphalan. Methods: Patients received test‐dose melphalan (10% of planned full‐dose) prior to conditioning. Blood samples for PK were obtained around test and full‐dose melphalan (140 mg/m2 or 4.7 mg/kg in patients <10 kg). Melphalan concentration was measured by liquid chromatography electrospray ionization tandem mass‐spectrometry assay and data were analysed using a population‐PK model and Bayesian estimation. Test and full‐dose melphalan clearance estimates were evaluated by pairwise Wilcoxon test and Bland–Altman plot. Results: Twenty‐four patients undergoing 25 transplants were included in the final analysis. Patients received standard full‐dose melphalan in 17 transplants, with median area under the concentration–time curve (AUC) of 5.5 mg*h/L (range, 3.0–9.5 mg*h/L). Patients received test‐dose melphalan in 23 transplants with a test‐dose PK predicted full‐dose AUC range of 2.9–16.8 mg*h/L. In seven transplants where patients had baseline organ impairment, test‐dose PK predicted higher exposure for standard full‐dose (median AUC 13.8 mg*h/L). Melphalan full‐dose was adjusted in these patients, with achievement of desired target AUC (3.6–5.4 mg*h/L) and no excess toxicity. Mean ratio of test‐dose clearance to full‐dose clearance was 1.03. Twenty of 22 patients (91%) were within the 95% confidence intervals of the clearance ratio. Conclusion: Melphalan test‐dose PK reliably predicts full‐dose PK and allows for accurate adjustment of full‐dose melphalan in RIC‐HCT for NMD. This approach can avoid excess toxicity from increased systemic exposure, especially in patients with organ impairment. [ABSTRACT FROM AUTHOR]

Summary: Myelofibrosis (MF) is a clonal stem cell neoplasm with heterogeneous clinical phenotypes and well‐established molecular drivers. Allogeneic haematopoietic stem cell transplantation (HSCT) offers an important curative treatment option for primary MF and post‐essential thrombocythaemia/polycythaemia vera MF or secondary MF. With a disease course that varies from indolent to highly progressive, we are now able to stratify risk of mortality through various tools including patient‐related clinical characteristics as well as molecular genetic profile. Owing to the high risk of mortality and morbidity associated with HSCT for patients with myelofibrosis, it is important to improve patient selection for transplant. Our primary goal is to comprehensively define our understanding of current practices including the role of Janus Kinase (JAK) inhibitors, to present the data behind transplantation before and after leukaemic transformation, and to introduce novel personalization of MF treatment with a proposed clinical‐molecular prognostic model to help elucidate a timepoint optimal for consideration of HSCT. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo- HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (cGVHD) remains a significant source of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Post-transplant, prophylactic rituximab has successfully decreased cGHVD rates in clinical trials, but the durability of this strategy is uncertain. The long-terms effect of post-HCT B cell depletion on immune reconstitution, B cell function, and infectious complications are also unknown. In this study, we provide 10 yr follow-up and correlative analyses on patients given post-HCT, prophylactic rituximab. The objective of the study is to examine the durability of cGVHD protection as well as the long-term effect of rituximab prophylaxis on protective immune reconstitution, B cell function, and alloantibody formation. We analyzed 35 patients given prophylactic rituximab on phase II clinical trial. Clinical outcomes included cGVHD development, relapse and survival outcomes, and infectious outcomes. Correlative analyses included B cell subset analysis, development of antibodies to infectious antigens, and, for male patients receiving female donor grafts, development of antibodies to HY antigens. To further investigate the effect of rituximab on immune reconstitution and function, we also analyzed 43 similarly transplanted patients who did not receive post- or peri-HCT rituximab as a comparator group. For patients who received rituximab, the 8-yr cumulative incidence of cGHVD and freedom from immunosuppression were 20.0% and 76.2%, respectively. Importantly, no late incidences of cGVHD developed beyond 14 mo post-HCT. Relative to patients who did not receive rituximab, post-HCT rituximab was associated with increased B cell aplasia at 1 yr post-HCT (42.9% versus 11% of patients, P = .037); by 3 yr post-HCT, this aplasia resolved. Patients who received rituximab also had a significantly lower proportion of IgD+/CD38+ transitional B cells at 3 yr post-HCT (78.8% versus 89.9%, P = .039); at 10 yr post-HCT, this percentage remained markedly decreased at 50.7%. Rituximab prophylaxis altered B cell function. In male patients receiving female donor grafts, fewer patients developed HY antibodies at 3 yr post-HCT (20% versus 78%, P = .04). At 10 yr post-HCT, HY antibody production remained decreased at 33%. Rituximab prophylaxis was also associated with significantly lower antibody response to tetanus and EBV infectious antigens as well as lower IgG levels. Despite these changes, post-HCT was not associated with increased infections, although patients who received rituximab required intravenous immunoglobulin (IVIG) supplementation more frequently than those who did not (62.9% versus 32.6% of patients, P = .01). Prior data on the efficacy and feasibility of rituximab prophylaxis are durable, with persistent reduction in cGVHD. Rituximab prophylaxis also results in lasting B cell immunologic changes, with altered B cell subset composition and decreased alloantibody formation. Associated infectious risks were not increased, perhaps mitigated by high IVIG use., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

This article describes the nursing experience of a single-arm allograft case. The nursing period lasted from March 13 to 21, 2018. With Gordon's functional health patterns as the framework for assessment, the author collected data by observing and interviewing the patient. Nursing problems including acute pain, risk for infection, impaired physical mobility, and anxiety were assessed. The results showed that all of the following can increase the success rate of transplantation: Establish a good relationship during the care process, divert attention to relieve pain, perform sterile wound care and assess changes in allogeneic arms, provide protective isolation and centralized care, provide transplant information, design aids to increase physical activity, encourage the expression of ideas and psychological support, listen, relieve anxiety, assist with adapting to physical changes, and face treatment with a positive attitude. Transplant observations focused on skin rash, monitoring immune data, avoiding serious rejection, immediate notifications, and daily team meetings to determine appropriate medical treatment. It is hoped by that sharing this experience, it can be used as a reference for providing clinical nursing care. [ABSTRACT FROM AUTHOR]

Introduction: Reducing toxicities while preserving efficacy in allogeneic stem cell transplant (allo-HCT) remains a particularly challenging problem. Different strategies to enhance the antitumor activity without increasing early and late adverse toxicities of the conditioning regimens have been investigated. Methods: The aim of "AlloTreo" prospective phase 2 clinical trial was to evaluate the efficacy and safety of a conditioning regimen based on Treosulfan (42 g/m2) and fludarabine (https://clinicaltrials.gov/ct2/show/NCT00598624). We enrolled 108 patients with hematological diseases who received a first allo-HCT between June 2005 and January 2011, inside the frame of this trial at our center. Median age at allo-HCT was 49 (21–69) years. Disease Risk Index was low in 14 (13%) patients, intermediate in 73 (67.7%), high in 17 (15.7%), and very high in 4 (3.7%). Donors were human leukocyte antigen (HLA)-matched related in 50 cases, 10/10-matched unrelated in 36, and 9/10-mismatched unrelated in 22. Graft- versus -host disease (GvHD) prophylaxis consisted of cyclosporine-A and methotrexate. Anti-T-lymphocyte globulin (ATLG) was administered in patients receiving unrelated allo-HCT. Stem cell source was mainly peripheral blood stem cells (95%). Results: Conditioning regimen was well tolerated. Full donor chimerism was documented for most patients (88%) at day +30. At 12 years, overall survival (OS) was 41.7% (32.2%–50.9%), progression-free survival (PFS) was 31.7% (23%–40.7%), GvHD-free/relapse-free survival was 20.9% (13.7%–29.1%), cumulative incidence (CI) of relapse was 44.5% (34.9%–53.6%), and transplant-related mortality (TRM) was 22.5% (15.1%–30.9%). CI of acute GvHD grades II–IV was 27.8% (19.7%–36.5%) at 100 days; 12-year CI of chronic GvHD was 40.7% (31.3%–49.9%). Relevant long-term adverse effects were 10 secondary malignancy, 3 fatal cardiovascular events, and 1 late-onset transplant-associated thrombotic microangiopathy. Ten successful pregnancies were reported after allo-HCT. In multivariate analysis, older age (≥60 years) at transplant [hazard ratio (HR), 2.157; p = 0.004] and a high/very high disease risk index (HR, 1.913; p = 0.026) were significantly associated with a lower OS. Conclusions: Overall, our data confirmed the myeloablative potential and safe toxicity profile of full dose Treo (42 g/m2) especially for the younger population. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplant (alloSCT) can overcome the adverse prognosis of chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its applicability remains unclear. Since 2007, our leukemia service has referred patients with 17p- CLL for alloSCT at presentation. In this study, the outcomes of these patients were reviewed retrospectively to determine whether they underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients with 17p- CLL who were referred to the transplant service from 2007 to 2010 were identified. Of these patients, 32 (62%) did not undergo alloSCT, mainly because of treatment- or disease-related complications (n = 15). The 2-year post-referral overall survival rates of the alloSCT and non-SCT groups were 64% and 25%, respectively (p = 0.001). These findings suggest that while alloSCT is an effective therapy in patients with 17p- CLL, pre-SCT complications may preclude a significant proportion of patients from undergoing the procedure.

IntroductionReducing toxicities while preserving efficacy in allogeneic stem cell transplant (allo-HCT) remains a particularly challenging problem. Different strategies to enhance the antitumor activity without increasing early and late adverse toxicities of the conditioning regimens have been investigated.MethodsThe aim of “AlloTreo” prospective phase 2 clinical trial was to evaluate the efficacy and safety of a conditioning regimen based on Treosulfan (42 g/m2) and fludarabine (https://clinicaltrials.gov/ct2/show/NCT00598624). We enrolled 108 patients with hematological diseases who received a first allo-HCT between June 2005 and January 2011, inside the frame of this trial at our center. Median age at allo-HCT was 49 (21–69) years. Disease Risk Index was low in 14 (13%) patients, intermediate in 73 (67.7%), high in 17 (15.7%), and very high in 4 (3.7%). Donors were human leukocyte antigen (HLA)-matched related in 50 cases, 10/10-matched unrelated in 36, and 9/10-mismatched unrelated in 22. Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine-A and methotrexate. Anti-T-lymphocyte globulin (ATLG) was administered in patients receiving unrelated allo-HCT. Stem cell source was mainly peripheral blood stem cells (95%).ResultsConditioning regimen was well tolerated. Full donor chimerism was documented for most patients (88%) at day +30. At 12 years, overall survival (OS) was 41.7% (32.2%–50.9%), progression-free survival (PFS) was 31.7% (23%–40.7%), GvHD-free/relapse-free survival was 20.9% (13.7%–29.1%), cumulative incidence (CI) of relapse was 44.5% (34.9%–53.6%), and transplant-related mortality (TRM) was 22.5% (15.1%–30.9%). CI of acute GvHD grades II–IV was 27.8% (19.7%–36.5%) at 100 days; 12-year CI of chronic GvHD was 40.7% (31.3%–49.9%). Relevant long-term adverse effects were 10 secondary malignancy, 3 fatal cardiovascular events, and 1 late-onset transplant-associated thrombotic microangiopathy. Ten successful pregnancies were reported after allo-HCT. In multivariate analysis, older age (≥60 years) at transplant [hazard ratio (HR), 2.157; p = 0.004] and a high/very high disease risk index (HR, 1.913; p = 0.026) were significantly associated with a lower OS.ConclusionsOverall, our data confirmed the myeloablative potential and safe toxicity profile of full dose Treo (42 g/m2) especially for the younger population.

Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.

Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome. [ABSTRACT FROM AUTHOR]

Relapse and graft failure after autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT) are serious and frequently fatal events. A second HSCT can be a life‐saving alternative, however, information on the results of such intervention in an outpatient setting is limited. Outpatient second hematoprogenitors transplant after reduced‐intensity conditioning (RIC) at a single academic center was analyzed. Twenty‐seven consecutive adults who received an allo‐HSCT after an initial auto‐ or allo‐HSCT from 2006 to 2019 were included. Data were compared using the χ2‐test. Survival analysis using Kaplan–Meier and Cox proportional hazard models was performed; cumulative incidence estimation of transplant‐related mortality (TRM) was assessed. Hodgkin lymphoma was the most frequent diagnosis for the group with a first auto‐HSCT with 5/12 (41.7%) cases, and acute myeloid leukemia for those with a first allo‐HSCT with 6/15 (40%). One‐year overall survival and disease‐free survival (DFS) was 66.7% (95% CI 27.2–88.2) and 59% (95% CI 16–86) for 12 patients with a first auto‐HSCT; and for 15 patients with a first allo‐HSCT, it was 43.3% (95% CI 17.9–66.5) and 36% (95% CI 13.2–59.9), respectively. Eight (29.6%) patients died of TRM and the cumulative incidence of TRM at 1 year was 22% (95% CI 8.6–39.27). Chronic graft‐versus‐host disease and late (>10 months) second transplantation were protective factors for longer survival. Neutropenic fever was more common in the group with a first allo‐HSCT (p = 0.01). In conclusion, outpatient second allo‐HSCT using RIC after auto‐ or allografting failure or relapse is feasible and offers a reasonable alternative for patients with severe life‐threatening hematological diseases. [ABSTRACT FROM AUTHOR]

T cell depletion by CD34+ cell selection of hematopoietic stem cell allografts ex vivo reduces the incidence and severity of GvHD, without increased risk of relapse in patients with acute leukemia in remission or MDS. The optimal candidate for CD34+‐selected HCT remains unknown, however. Objective: To determine outcomes based on both disease‐ and patient‐specific factors, we evaluated a prognostic model combining the Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT‐CI), an approach recently shown to predict overall survival in a broad population of allograft recipients (Kongtim P, Parmar S, Milton DR, et al. Impact of a novel prognostic model, hematopoietic cell transplant‐composite risk (HCT‐CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant. 2019;54(6):839‐48). Methods: This was a retrospective analysis of 506 adult recipients of first allogeneic HCT with CD34 + selected PBSCs from 7/8‐ or 8/8‐matched donors for AML (n = 290), ALL (n = 72), or MDS (n = 144). The Kaplan‐Meier method estimated OS and RFS. The cumulative incidence method for competing risks estimated relapse and non‐relapse mortality (NRM). We evaluated the univariate association between variables of interest and OS and RFS using the log‐rank test. Cox regression models assessed the adjusted effect of covariates on OS/RFS. Results: Stratification of patients based on a composite of DRI (low/intermediate vs high/very high) and HCT‐CI (0‐2 vs ≥3) revealed differences in OS and RFS between the four groups. Compared with reference groups of patients with low/intermediate DRI and low or high HCT‐CI, those with high DRI had a greater risk of death (HR 2.30; 95% CI 1.39, 3.81) and relapse or death (HR 2.50; 95% CI 1.55, 4.05) than patients with any HCT‐CI but low/intermediate DRI (HR death 1.80; 95% CI 1.34, 2.43; HR relapse/death 1.68; 95% CI 1.26, 2.24). Conclusions and Clinical Implications: A model combining DRI and HCT‐CI predicted survival after CD34+ cell‐selected HCT. Application of this combined model to other cohorts, both in retrospective analyses and prospective trials, will enhance clinical decision making and patient selection for different transplant approaches. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation can be curative for children with difficult-to-treat leukemia. The conditioning regimen utilized is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children's Hospital, consisting of busulfan (with pharmacokinetic target of 3750 μmol*min/L/day ±10%) for 4 days, higher dose (250 mg/m 2 ) fludarabine and 400 centigray (cGy) of total body irradiation., Procedure: This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical., Results: Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median [interquartile range] time of 14 days [8-30 days]. The cumulative incidence of acute graft-versus-host disease was 44.8% [95% confidence interval, CI: 35.6%-54.0%], while chronic graft-versus-host disease was noted in 16.0% [95% CI: 8.7%-23.3%]. At 2 years, the overall survival was 78.1% [95% CI: 70.8%-86.4%] and event-free survival was 74.7% [95% CI: 66.4%-83.0%]. Cumulative incidence of relapse was 11.3% [95% CI: 5.1%-17.5%]. There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group., Conclusion: Our conditioning regiment for children with ALL resulted in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting busulfan dose in this cohort did not result in improved outcomes., (© 2024 Wiley Periodicals LLC.)

• Allogeneic stem cell transplantation (SCT) did not offer a significant survival advantage over autologous SCT. • Relapse with progressive disease was the main cause of death. • Patients with PCL should be included in clinical trials of novel immunotherapies. Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (auto) or allogeneic (allo) stem cell transplantation (SCT) is not clear, given the lack of clinical trial-based evidence. This single-center retrospective study describes the outcomes of 16 patients with PCL (n = 14 with primary PCL) who underwent either autoSCT (n = 9) or alloSCT (n = 7) for PCL in the era of novel agents, between 2007 and 2019. The median age of the cohort was 58 years. High-risk cytogenetics were found in 50% of the patients. All patients received a proteasome inhibitor and/or immunomodulatory drug-based regimen before transplantation. At the time of transplantation, 10 patients (62%) obtained at least a very good partial response (VGPR). The response after autoSCT (3 months) was at least a VGPR in 6 patients (67%; complete response [CR] in 5). All patients undergoing alloSCT achieved a CR at 3 months. Maintenance therapy was provided to 5 patients (56%) after autoSCT. The median progression-free survival after transplantation was 6 months in the autoSCT group, compared with 18 months in the alloSCT group (P =.09), and median overall survival (OS) after transplantation in the 2 groups was 19 months and 40 months, respectively (P =.41). The median OS from diagnosis was 27 months and 49 months, respectively (P =.50). Of the 11 deaths, 10 patients (91%) died of relapsed disease. AlloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, in agreement with recent reports, and relapse remains the primary cause of death in these patients. [ABSTRACT FROM AUTHOR]

• A tapering strategy should be used to discontinue ruxolitinib in transplant recipients. • Ruxolitinib should be continued until conditioning given the risk of cytokine rebound. • Ruxolitinib is well tolerated if continued through conditioning therapy and until engraftment. • Patients on ruxolitinib must be monitored closely for cytomegalovirus reactivation and cytopenias. Ruxolitinib is an oral JAK1/2 inhibitor that is approved for use in patients with intermediate and high-risk myelofibrosis (MF) based on its proven spleen and symptom burden reduction. Its impact on hematopoietic stem cell transplantation (HSCT) outcomes is largely unknown, however. A significant number of patients proceeding to HSCT have been treated with ruxolitinib, and the specifics of its peritransplantation use vary widely in the published literature. Here we review the currently published data and experience to guide management of patients with MF on ruxolitinib proceeding to HSCT. [ABSTRACT FROM AUTHOR]

Background: Busulfan (BU) in combination with cyclophosphamide (CY) is used as an effective conditioning regimen in hematopoietic SCT. Busulfan, depletes glutathione level in liver and causes elevated levels of CY metabolites. Cyclophosphamide metabolites are highly toxic for sinusoidal endothelial cells and cause VOD/ SOS with high mortality rate. Materials and Methods: All adult patients with acute leukemia, who were candidates for myeloablative allogenic SCT admitted in Stem Cell Transplantation center of our center were enrolled in this prospective randomized clinical trial during 2 years. We tested the hypothesis that reverse administration from BU-CY (28 patients) to CY-BU group (27 patients) would reduce liver toxicity. Results: Liver function tests were significantly higher in BU-CY group between day -1 and +4 (p

Abstract Background GATA2 deficiency presents with a spectrum of phenotypes including increased susceptibility to viral and bacterial infections, multi-lineage cytopenias, aplastic anemia, leukemic transformation and lymphedema. Allogeneic transplantation is only curative therapy for GATA2 deficiency, but is associated with significant treatment related morbidity and mortality. Given the spectrum of clinical presentation, accurate diagnosis of GATA2 deficiency is necessary to identify patients early in their disease course when allogeneic bone marrow transplantation may be of clinical benefit. Case presentation In this report, we present a GATA2 mutation diagnosed in 23-year-old woman presenting with pancytopenia, recurring oral blisters, fatigue and chronic pain. We describe markedly low levels of mature B-cells in the blood and bone marrow and the absence of detectable blood dendritic cells with normal serum immunoglobulin levels and normal numbers of marrow plasma cells. She was ultimately diagnosed with GATA2 haplo-insufficiency due to a GATA2 germ-line mutation and underwent a successful allogeneic bone marrow transplant from a 10/10 HLA matched unrelated donor. Conclusions The case illustrates the diagnostic difficulties in identifying GATA2 deficiencies and the importance of family history and genetic testing. GATA2 plays an important role in B-cell and dendritic cell development, and decreased numbers of those cells is a characteristic feature that should prompt consideration of GATA2 deficiency in a patient with pancytopenia. Maturation of B-cells to long-lived plasma cells is relatively unaffected in GATA2 deficiency. Allogeneic stem cell transplantation can correct immune-deficiencies and prevent leukemic transformation in patients with GATA2 deficiency.

Hematopoietic stem cell transplant (HCT) is used with increasing frequency for the treatment of malignant and nonmalignant diseases. Thrombocytopenia is a common complication following HCT and is associated with decreased survival. Supportive care with platelet transfusion requires significant resources, reduces quality of life, and is associated with several adverse effects including transfusion reaction, infection, and alloimmunization. Thrombopoeitin receptor agonists (TPO‐RA) have been found to be safe and effective for the treatment of immune mediated thrombocytopenia, thrombocytopenia related to bone marrow failure syndromes, and thrombocytopenia of chronic liver disease. We hereby discuss in this review the evidence for use of TPO‐RA for the management of thrombocytopenia after HCT. [ABSTRACT FROM AUTHOR]

Aim: Hepatitis E Virus (HEV) infection is an emerging threat in allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) recipients. The aim of this study was to determine the prevalence of HEV infection in patients with acute leukemia before and after the transplantation. Material and Methods: The study was carried out with the serum samples taken before and after the transplantation from patients (n=42) with acute leukemia, who were 4 months to 64 years of age and who had allogenic transplant at Gazi University Hospital. All samples were tested in terms of HEV-specific anti-IgG and IgM positive value by using ELISA kit. Results: While 1 (2.3%) of the samples that were included in the study was positive anti-HEV IgG before transplantation, it was found negative after the transplantation (58th month). Positive anti-HEV IgM was not found before and after the transplantation in the collected samples. The average age of the seronegative group was determined as 30.8 ± 33.1 for male and female, respectively. There was no statistically significant difference in terms of anti-HEV IgM positivity and anti-HEV IgG positivity compared with seronegative cases of seropositive cases. Conclusions: This study was conducted to determine the prevalence of HEV infection in allogeneic stem cell patients. With this study, the incidence and importance of HEV can be determined in these patients before and after transplantation. This study can also create an important epidemiological data for our country. [ABSTRACT FROM AUTHOR]

Background: Busulfan (BU) in combination with cyclophosphamide (CY) is used as an effective conditioning regimen in hematopoietic SCT. Busulfan, depletes glutathione level in liver and causes elevated levels of CY metabolites. Cyclophosphamide metabolites are highly toxic for sinusoidal endothelial cells and cause VOD/SOS with high mortality rate. Materials and Methods: Between September 2013 and September 2015, all adult patients with acute leukemia who were candidates for myeloablative allogenic SCT and were admitted to Stem Cell Transplantation center were enrolled in this prospective randomized clinical trial. We tested the hypothesis that reverse administration from BU-CY (n=28) to CY-BU group (n=27) would reduce liver toxicity. Results: Liver function tests were significantly higher in the BU-CY group between day -1 and +4 (p<0.05), but VOD/SOS was not diagnosed in both groups. The incidence and severity of acute GVHD was higher in the BU-CY group, but not statistically significant. Engraftment and mortality rate were not different. Conclusion: These data support the concept that CY-BU is associated with less liver toxicity, suggesting CY-BU is superior to BU-CY as conditioning. [ABSTRACT FROM AUTHOR]

• HCT outcomes were analyzed in r/r ALL patients, after salvage with blinatumomab. • Pre-HCT blinatumomab was given for morphologic (n = 24) or MRD-positive disease (n = 11). • No unusual toxicities or delayed engraftment was observed post-HCT. • Subgroup analysis (MRD/cytogenetics) showed no significant difference in survival. • Blinatumomab may be considered as a safe and effective salvage therapy pre-HCT. Historically, outcomes of adult patients with relapsed acute lymphoblastic leukemia (ALL) who fail to enter remission with conventional chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. Although allogeneic hematopoietic cell transplant (HCT) is the recommended consolidation therapy for patients with r/r ALL who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown. We treated 89 patients with r/r ALL with blinatumomab, of whom 43 patients (48%) achieved remission. Here we describe our single-center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross (n = 24) or minimal residual disease (n = 11) before HCT. Overall survival at 1 and 2 years after allogeneic HCT was 77% and 52%, respectively. Leukemia-free survival at 1 and 2 years were 65% and 40%, respectively. Additionally, with blinatumomab administration pre-HCT, no unusual toxicities such as delayed neutrophil/platelet engraftment or graft failure were observed. Acute grades II to IV graft-versus-host disease (GVHD) at day +100 post-HCT was at 43% and 2-year chronic GVHD was 36%, both comparable with historic control subjects. Finally, results of our subset analysis based on pre-HCT minimal residual disease (MRD) status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD-negative status and the entire cohort. In conclusion, based on results of this study, blinatumomab may be considered as a safe and effective agent for r/r ALL patients before HCT. [ABSTRACT FROM AUTHOR]

As with other hematologic malignancies, the management of patients with MF has very much entered the molecular era. The prognostic impact of several driver and nondriver mutations is now well‐established; this has obvious relevance to both patient selection for allogeneic hematopoietic cell transplantation and posttransplant outcomes. For transplant, present JAK2 or triple‐negative driver mutation genotype together with present ASXL1 mutation may provide best utility for counseling patients with respect to posttransplant outcome, together with clinical (performance status, age, and leukocyte and platelet counts) and transplant‐related factors (donor relation). Different conditioning intensities do not seem to play a role with regards to outcome posttransplant but still need to be compared in the molecular era. While ruxolitinib provides clinical benefits for patients before transplant, more studies on the finetuning and integration of ruxolitinib into the transplant algorithm are needed. In conclusion, as clinically important risk stratification has been achieved throughout the disease course and new targeted agents become increasingly available, a collaborative and integrative approach is needed to translate new biological insights to personalized/tailored and timed therapy for patients with myelofibrosis. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). Reduced intensity regimens, alternative graft sources, advances in HLA‐matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have led to a wider application of allo‐HSCT to eligible patients. Unfortunately, 30‐40% of patients with AML will relapse after transplant and this is the major cause of treatment failure. Careful consideration should be paid in choosing the type of graft, graft source, and conditioning regimen to minimize the risk of disease recurrence. In addition, maintenance therapy following allo‐HSCT is a potential method to keep the disease in remission, especially in those with high‐risk disease characteristics. Pharmacological targeted agents with low side effect profile such as tyrosine kinase inhibitors, hypomethylating agents (HMAs), HDAC inhibitors, antibody drug conjugates (ADCs), isocitrate dehydrogenase inhibitors, and hedgehog inhibitors may prevent relapse in posttransplant setting and are under investigation. Immunological therapies including donor lymphocyte infusions (DLIs), natural killer (NK) cell therapy, peptide vaccine targeting tumor antigens, and adoptive T‐cell therapies all hold promises in this area as well. As targeted agents and immunotherapies continue to be developed, patients at high risk of recurrence may benefit from prophylactic maintenance therapy. Here we review the current landscape in this rapidly evolving clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim of this study was to evaluate survival outcomes following allo‐HCT in myelodysplastic syndrome (MDS), and the secondary aim was to study variables impacting survival. Methods: This analysis describes patient characteristics, treatment, and outcomes in 125 consecutive adult patients with MDS transplanted from 2005 to 2018. Results: The median age was 61 years, and median follow‐up in patients alive at last follow‐up was 29 months. The 2‐year OS and RFS were 39% (95%CI 30%‐48%) and 35.3% (95% CI: 27%‐44%), respectively. Transfusion dependence, high‐risk cytogenetics, and high serum ferritin were independent risk factors for death. The cumulative incidence of relapse (CIR) and non‐relapse mortality (NRM) at 2 years were 23% and 41.6%, respectively. High serum ferritin was significantly associated with NRM. There was no association between the percentage of bone marrow blasts (either at diagnosis or at pretransplant evaluation), on relapse or survival. Induction chemotherapy did not offer any survival advantage in MDS RAEB‐2 patients compared to cytoreduction with azacytidine alone. Conclusion: Our results highlight the importance of karyotype on survival after allo‐HCT and identify serum ferritin and transfusion dependence as important surrogate markers of outcome. In addition, our results demonstrate the efficacy of azacytidine for pretransplant cytoreduction. [ABSTRACT FROM AUTHOR]

With several different CAR T cell therapies under advanced phases of clinical trials, and the first FDA-approved CAR treatments in 2017 (Yescarta and Kymriah), CAR T cell therapy has become one of the most promising therapies for the treatment of certain types of cancer. This success has bred an opportunity to optimize the production of CAR T cells for easier patient access. CAR T cell therapy is a rather expensive and personalized process that requires expensive measures to collect cells from patients, engineer those cells, and re-infuse the cells into the patient with adequate quality controls at each phase. With this in mind, significant attempts at creating a "universal" CAR T cell are underway in order to create an "off-the-shelf" product that would reduce the expense and time required for traditional CAR T cell treatment. The primary obstacle facing this endeavor is avoiding graft-versus-host disease that accompanies allogeneic transplants between genetically dissimilar individuals. With the advent of CRISPR and TALEN technology, editing the genome of allogeneic cells has become very possible, and several groups have provided initial data analyzing the effects of CAR T cells that have been edited to avoid host rejection and avoid endogenous TCR alloreactivity. These engineered cells not only have to avoid GVHD but also have to retain their anti-tumor efficacy in vivo. Here, we expand on the recent efforts and strides that have been made in the design and testing of universal allogeneic CAR T cells. [ABSTRACT FROM AUTHOR]

Chronic cutaneous graft-versus-host disease (GVHD) is most frequently expressed in the skin. The sclerotic type presents difficulty in its management, since the multiple immunosuppressive systemic therapies to improve it are not always effective and increase the risk of infections. CLINICAL CASE: A 57-year-old male patient, in whom in January 2013 the diagnosis of acute lymphoblastic leukemia was established, which achieved complete remission after three cycles of chemotherapy with the HyperCVAD scheme. Five months later an allogeneic transplant of hematopoietic stem cells from related living donor (sibling) was performed as consolidation treatment. He received oral tacrolimus and mycophenolate oral as a prophylaxis of GVHD. Subsequently, Epstein-Barr virus infection (positive serology and PCR) was documented, so immunosuppressive management was discontinued. Ten months after the transplant, the patient started with generalized musculoskeletal pain, as well as oral, genital and ocular mucositis, for which he received treatment with unspecified creams and eye drops. Two months later he began with exulceration on the back of the neck, as well as maculo-papular rash on the head and trunk, remaining unchanged for four months. The diagnosis of graft disease against chronic host was established. CONCLUSION: Through a case with extensive sclerosis, we illustrate the beneficial management and proper tolerance of UVA phototherapy associated with oral psoralen (PUVA), avoiding other therapies and their adverse concomitant effects. [ABSTRACT FROM AUTHOR]

Objective: The primary objective was to assess the effect of central nervous system involvement in acute myeloid leukemia (CNS‐AML) on outcomes after allogeneic hematopoietic stem cell transplant (allo‐HCT). The secondary objective was to assess the utility of pretransplant cerebrospinal fluid (CSF) assessment in AML. Methods: We retrospectively analyzed survival outcomes in 338 adult AML patients (with and without CNS‐AML) after allo‐HCT. CNS involvement was defined as clinical, pathological, or radiological evidence of CNS involvement any time after diagnosis. Results: The median follow‐up in surviving patients was 23.7 months. Twenty‐five patients (7.4%) had prior history of CNS disease, with normal CSF pretransplant. Three patients had CSF blasts detected for the first time at pretransplant evaluation (0.88%). The 2‐year OS and RFS in groups with and without CNS involvement were not significantly different. Patients with CNS‐AML had significantly higher 1‐year cumulative incidence of relapse (29.7% vs 16.9%, P = .048). Age more than 65 years and absence of marrow remission at transplant were significant adverse factors for survival. Conclusion: CNS‐AML is not an independent risk factor for survival after allo‐HCT, but can be associated with higher relapse rates. Pretransplant CSF assessment has low yield in detecting new CNS disease pretransplant in AML. [ABSTRACT FROM AUTHOR]

Limited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu–Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown. The purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu–Mel compared to a historical control group. This was a retrospective, single-center, cohort review of 123 patients who received a Flu–Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic. The median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31–3.60] vs 3.31 doses [1.61–4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3–122.7] vs 26.2 h [14.7–48.1]; p = 0.016). The combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu–Mel-based preparative regimen. • Use of palonosetron, fosaprepitant, and olanzapine decreased rescue antiemetic use. • Palonosetron, fosaprepitant, and olanzapine prolonged time to first antiemetic. • Improves tolerability of transplant and therefore may increase access to transplant. [ABSTRACT FROM AUTHOR]