Allogeneic Hematopoietic Cell Transplant Patients Research Articles

Predictors of kidney complications and analysis of hypertension in children with allogeneic hematopoietic stem cell transplantation.

This study aimed to determine incidence of kidney complications in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients. Pediatric allogeneic HSCT patients were included. Post-transplantation urinary system complications were collected from medical records and glomerular filtration rates at last visit compared with clinical parameters. Additionally, 24-h ambulatory blood pressure monitoring was performed. The study included 165 pediatric patients. Acute kidney injury (AKI) developed in 125 (75.8%) patients of whom 54 (43.2%) had stage 1, 36 (28.8%) stage 2, and 35 (28%) stage 3 AKI. Primary malignant disease and viral infection post-HSCT were associated with increased risk of AKI (OR: 4; 95%CI: 1.2-13, p = 0.022 and OR: 2.9; 95%CI: 1.2-6.8, p = 0.014, respectively). Mean duration of post-HSCT follow-up was 4.4 ± 2.5 years, during which time 8 patients had chronic kidney disease (CKD) (stage 1, 4 patients; stage 2, 3 patients; stage 3, 1 patient). CKD incidence was higher in patients in whom stem cell product was bone marrow + cord blood and mobilized peripheral blood, compared to bone marrow alone (40-37.5% versus 5.1%, p = 0.002). Based on 24-h ABPM, 14.7% and 7.4% of patients with normal office blood pressure had pre-hypertension and hypertension, respectively. In patients with albuminuria/severe albuminuria, daytime and nighttime systolic SDS scores were higher than those without albuminuria/severe albuminuria (p = 0.010 and p = 0.004, respectively). Incidence of AKI is higher in pediatric HSCT patients with primary malignant disease and those with documented viral infection. Our study highlights the beneficial role of 24-h ABPM as a routine part of standard care of pediatric HSCT recipients.

Unresolved issues in allogeneic hematopoietic cell transplantation for non-malignant diseases.

Allogeneic hematopoietic cell transplantation (HCT) can be curative for a variety of non-malignant diseases (NMDs) as well as hematological malignancies. However, there are several fundamental differences between HCT for NMDs and hematological malignancies, which may necessitate the use of alternative HCT strategies. For example, these diseases differ in the intensity of conditioning regimen sufficient to improve disease. In addition, patients with NMDs are at higher risk of graft failure or mixed chimerism following HCT, and gain no or little survival benefit from graft-versus-host disease. Because more than 80% of patients with NMDs become long-term survivors, greater attention has been paid to late adverse effects and decreased of quality of life after HCT. This review addresses several unresolved issues in allogeneic HCT for patients with NMDs, such as (1) stem cell source, (2) conditioning regimen, (3) use of serotherapy or low-dose irradiation, and (4) therapeutic intervention for mixed chimerism. Resolving these issues may improve transplant outcomes in patients with NMDs.

Neurological complications in adult allogeneic hematopoietic stem cell transplant patients: Incidence, characteristics and long-term follow-up in a multicenter series.

Neurological complications (NCs) represent a diagnostic and clinical challenge in allogeneic hematopoietic stem cell transplant (alloHSCT) patients. We retrospectively analyzed NC incidence, etiology, timing, characteristics, outcome, and long-term effects in 2384 adult patients transplanted in seven Italian institutions between January 2007 and December 2019. Ninety-three (3.9%) patients were affected by 96 NCs that were infectious (29.2%), immune/inflammatory (26%), drug-related (12.5%), cerebrovascular (5.2%), metabolic (3.1%), related to central nervous system disease relapse (11.5%) and malignancy (3.1%), or undefined (9.4%). Six patients (6.4%) had neurological manifestations of chronic graft-versus-host disease (GVHD). NCs occurred on average at day +128 (from -5 to +4063). Early (< day +120) and late NCs had similar frequencies (46.9% vs 53.1%, p = 0.39). Thirty-one patients (33.3%) were affected by acute or chronic GVHD at the NC onset. With a median follow-up of 25.4 (0.4-163) months, the overall mortality due to NCs was 22.6%. The median time between NC onset and death was 36 (1-269) days. Infectious NCs were the main cause (61.9%) of NC-related mortality. A persistent neurological impairment occurred in 20.4% patients, 57.9% of whom being affected by immune/inflammatory NCs. This study highlights the rare, yet severe impact of alloHSCT-associated NCs on patient survival and long-term functional ability.

Circulating endothelial cells and endothelial progenitor cells as potential predictors of acute GVHD after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a major cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation. Endothelial cell damage may trigger the initiation of aGVHD. Endothelial damage and repair were evaluated by counting circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in 17 allogeneic hematopoietic stem cell transplantation patients at pre-conditioning, day 0, day 7, day 14, day 30, and day 60 by multicolor flow cytometry. Von Willebrand factor activity was simultaneously measured. Eight patients developed aGVHD and were compared to non-aGVHD patients. Patients' characteristics were not different, except for previous treatment courses. There was no difference in von Willebrand factor activity between the two groups. Both CEC and EPC counts were decreased on day 7 and day 14 and then increased thereafter. The CEC count on day 7 was significantly lower in the aGVHD group than in the non-aGVHD group (p=.0401). Restoration of the EPC count on day 60 was significantly suppressed in the aGVHD group (p=.0464). The CEC count on day 7 could predict aGVHD development (AUC 0.8214, p=.0372). The present results showed that CEC count on day 7 could be a predictor of aGVHD.

Evaluation of a group-based exercise and relaxation rehabilitation program during hospitalization for allogeneic hematopoietic stem cell transplant.

Exercise and relaxation interventions have demonstrated benefits in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients; however, little is known about the implementation enablers and barriers for inpatient rehabilitation or its impact on health outcomes. To conduct a program evaluation of group-based rehabilitation consisting of exercise and relaxation classes for allo-HSCT inpatients. Prospective program evaluation using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Inpatient hospital unit at a tertiary care center. Forty-five adult patients admitted for allo-HSCT. Standard of care rehabilitation. Program attendance, safety, satisfaction, and fidelity were assessed. Exploratory effectiveness analyses were conducted via the measurement of physical, psychosocial, clinical, and health resource use outcomes at hospital admission and discharge. Forty-seven of the 63 patients receiving allo-HSCT between November 2019 and March 2020 were consented. Data presented in this publication are from the 33 participants who completed study assessments (high attrition due to cancellation of research during the COVID-19 pandemic). Eighty-two percent of participants attended at least one class; however, 55% of the participants invited to the classes on a daily basis were not able to attend. Barriers to participation included transplant complications, isolation for infection prevention, and fatigue. There were no adverse events associated with the intervention and 82% of participants adhered to the prescribed activities. Participants reported satisfaction with the program and enjoyed the motivational support and social interaction. Between hospital admission and discharge, anxiety scores improved; however, fatigue, depression, grip strength, functional mobility, and quality of life scores declined. Physical activity volume and lower body strength were maintained. Group-based exercise and relaxation classes seem to be feasible and safe during hospitalization for allo-HSCT; however, there are pragmatic barriers to be considered for optimal program implementation. Further research examining program effectiveness and adoption is warranted.

Predicting Long-term Survival After Allogeneic Hematopoietic Cell Transplantation in Patients With Hematologic Malignancies: Machine Learning-Based Model Development and Validation.

BackgroundScoring systems developed for predicting survival after allogeneic hematopoietic cell transplantation (HCT) show suboptimal prediction power, and various factors affect posttransplantation outcomes.ObjectiveA prediction model using a machine learning–based algorithm can be an alternative for concurrently applying multiple variables and can reduce potential biases. In this regard, the aim of this study is to establish and validate a machine learning–based predictive model for survival after allogeneic HCT in patients with hematologic malignancies.MethodsData from 1470 patients with hematologic malignancies who underwent allogeneic HCT between December 1993 and June 2020 at Asan Medical Center, Seoul, South Korea, were retrospectively analyzed. Using the gradient boosting machine algorithm, we evaluated a model predicting the 5-year posttransplantation survival through 10-fold cross-validation.ResultsThe prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.788 (SD 0.03). Furthermore, we developed a risk score predicting probabilities of posttransplantation survival in 294 randomly selected patients, and an agreement between the estimated predicted and observed risks of overall death, nonrelapse mortality, and relapse incidence was observed according to the risk score. Additionally, the calculated score demonstrated the possibility of predicting survival according to the different transplantation-related factors, with the visualization of the importance of each variable.ConclusionsWe developed a machine learning–based model for predicting long-term survival after allogeneic HCT in patients with hematologic malignancies. Our model provides a method for making decisions regarding patient and donor candidates or selecting transplantation-related resources, such as conditioning regimens.

495 - Outcomes of COVID-19 Infection in Allogeneic Hematopoietic Stem Cell Transplant Patients Treated with Hyperbaric Oxygen: A Case Series

495 - Outcomes of COVID-19 Infection in Allogeneic Hematopoietic Stem Cell Transplant Patients Treated with Hyperbaric Oxygen: A Case Series

382 - Association of Tacrolimus Levels and Time from Transplant with Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Patients

382 - Association of Tacrolimus Levels and Time from Transplant with Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Patients

Optimized cyclosporine starting dose may reduce risk of acute GvHD after allogeneic hematopoietic cell transplantation: a single-center cohort study

Cyclosporine A (CsA) is commonly used for Graft versus Host Disease (GvHD) prophylaxis at a recommended starting dose of 3 mg/kg/d: Evidence for the effect of different CsA starting doses on GvHD risk is limited. We therefore estimated the association of 5 mg/kg/d (CsA5) and 3 mg/kg/d (CsA3) CsA starting doses with GvHD risk in two consecutive cohorts of allogeneic hematopoietic cell transplantation (allo-HCT) patients, exploring potential risk factors for incident acute GvHD, with a focus on CsA starting dose. We analyzed 519 patients within CsA5 (n = 153) and CsA3 (n = 366). The cumulative incidence function of acute GvHD grade ≥2 was higher in the CsA3 compared to the CsA5 group (41% vs. 33%, respectively; p = 0.043), without impacting chronic GvHD. In multivariable analysis, a CsA starting dose of 3 mg/kg/d, no ATG use, unrelated donor and high to very high disease risk index were significantly associated with acute GvHD grade ≥2. A higher CsA starting dose of 5 mg/kg/d was independently associated with lower acute GvHD risk, and higher CsA levels in the early period after allo-HCT were reached.

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults.

Ruxolitinib, a JAK1/2 inhibitor, is used to treat chronic graft versus host disease (cGVHD) in adult allogeneic hematopoietic stem cell transplant patients, but experience in children is limited, perhaps because of lack of pediatric dosing information. In this report, we describe our pediatric and young adult dosing strategy experience in cGVHD. Ruxolitinib was administered orally at 5 mg twice daily for children ≥25 kg or 2.5 mg twice daily if <25 kg. The dose was halved with concurrent azole administration and increased to a maximum of 10 mg twice daily if tolerated. Responses were evaluated using the 2014 NIH consensus criteria. Phosphorylation of lymphocyte STAT5 following dosing, a surrogate of JAK inhibition, was evaluated by flow cytometry. Twenty patients with a median age 14.6 y (range 5-26 y) received ruxolitinib for severe (n = 9) and moderate (n = 11) cGVHD. Median steroid dose was 0.5 mg/kg/d (range 0.08-1.5 mg/kg/d) at ruxolitinib initiation. Two patients with moderate cGVHD achieved a complete response (CR), while 12 patients achieved a partial response (PR) at a median of 48 d (range 17-98 d) from the first ruxolitinib dose, for an overall response rate of 70%. Eleven patients are maintaining their PRs. pSTAT5 on lymphocytes was absent or decreased (0%-6% events) in 5 evaluated patients, suggesting adequate inhibition. Three patients discontinued ruxolitinib because of neutropenia, thrombocytopenia, or elevated alanine aminotransferase. Four patients developed bacterial infections, and 3 experienced symptomatic viral infections. Two patients died from complications related to progressive severe cGVHD. Ruxolitinib using our dosing strategy demonstrates promise for treating cGVHD in children.

Pharmacogenomic prescribing opportunities in percutaneous coronary intervention and bone marrow transplant patients.

Aim: To evaluate the potential impact of preemptive multigene pharmacogenomic (PGx) testing on medication prescribing in real-world clinical settings. Patients & methods: Prescription frequencies for 65 medications with actionable PGx recommendations were collected in 215 percutaneous coronary intervention (PCI) and 131 allogeneic hematopoietic cell transplant (allo-HCT) patients. A simulation projected the number of PGx-guided prescribing opportunities. Results: In PCI and allo-HCT patients, respectively, 66.5 and 90.1% were prescribed at least one medication with actionable PGx prescribing recommendations. Simulations projected 26.5 and 41.2 total PGx-guided prescribing opportunities per 100 PCI and allo-HCT patients, respectively, if multigene PGx results were available. Conclusion: A multigene PGx testing strategy offers potential to optimize medication prescribing beyond clopidogrel and tacrolimus in PCI and allo-HCT patients.

Survey on delirium in allogeneic hematopoietic cell transplant patients at our hospital

Survey on delirium in allogeneic hematopoietic cell transplant patients at our hospital

Effect of Early Nutritional Support on Quality of Life by EORTC QLQ-C30 in Allogeneic Hematopoietic Stem Cell Transplantation.

Increasing attention is being paid to the importance of nutritional management of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. However, few studies have conducted detailed evaluations of both nutritional intake and quality of life (QOL) in allo-HSCT patients. Therefore, we investigated the nutritional status and quality of life of our allo-HSCT patients. The subjects were 26 adults who underwent allo-HSCT at Hamamatsu University Hospital between August 2018 and October 2021. Early nutritional intervention was provided from the time of the decision to perform allo-HSCT to the time of discharge, and it incorporated regular QOL assessments. The analyzed indices were nutritional intake, anthropometric measurements, body mass index (BMI), grip strength, body composition analyzer (InBody S10) measurements, and blood laboratory values including transthyretin levels. QOL was assessed using the QLQ-C30 questionnaire of the European Organization for Research and Treatment of Cancer (EORTC) (version 3.0) and calculated according to the EORTC scoring manual. The indices were compared at pre-transplantation, 30 days post-transplantation, 60 days post-transplantation, and at discharge. The association between pre-transplantation nutritional status and QOL was examined. The median hospital stay after transplantation was 97 days (range, 78-123 days). Energy intake was maintained at 31 kcal/day/kg through 30 days post-transplantation, 60 days post-transplantation, and discharge, and protein intake was maintained at 1.0 g/day/kg throughout all time periods. There was a significant positive correlation between the pre-transplantation transthyretin level and the 60-day post-transplantation QOL scores for "global health", "physical functioning", "cognitive functioning", and "emotional functioning", and there were significant negative correlations with "fatigue" and "pain" that indicated improvement. Early nutritional management of allo-HSCT patients prior to transplantation allowed maintenance of nutritional intake, and higher pre-transplant transthyretin levels were associated with higher QOL scores at 60 days post-transplantation.

Comparison of Outcomes After Second Allogeneic Hematopoietic Cell Transplantation Versus Donor Lymphocyte Infusion in Allogeneic Hematopoietic Cell Transplant Patients

BackgroundAllogeneic hematopoietic cell transplantation (HCT) is potentially curative for hematological disease however can be complicated by relapse or graft failure (GF), for which second-HCT and donor lymphocyte infusions (DLI) are performed. This study aimed to compare outcomes following the two interventions. MethodsWe retrospectively investigated 89 patients with relapse or GF after first-HCT, 50 (56%) underwent second HCT and 39 (44%) received (DLI), from June 2011 to September 2020. ResultsMedian age at intervention was 55 years (19-72). Second-HCT was performed for relapse in 19 patients and for GF in 31 patients (primary GF in 11 and secondary in 20 patients), same donor was used in 25 (50%) patients. DLI was performed for relapse in 20 and for secondary GF in 19 patients. Median number of DLI administered was 2 (range 1-11). Univariate analysis demonstrated 2 year overall survival (OS) for second-HCT was superior when performed for relapse (65%) compared to GF (44%) (P = .03). For DLI patients, 2 year OS was 49% for GF and 45% for relapse patients (P = .49). For relapse as an indication, second-HCT demonstrated borderline superiority compared to DLI (P = .07). Multivariable analysis demonstrated for OS for the entire cohort demonstrated donor mismatch (HR 0.50, 95% CI 0.26%-0.94%, P = .03), KPS at time of intervention (HR 2.10, 95% CI 1.14%-3.85%, P = .02) and time from first-HCT to intervention (HR 0.51, 95% CI 0.28%-0.93%, P = .03) as significant variables. ConclusionSecond-HCT may improve outcomes when performed for relapse post-transplant if patients achieve remission again, while DLI may be reserved for patients with active disease.

Association between CYP3A4, CYP3A5, and ABCB1 Genotype, Tacrolimus Concentrations, and Outcomes Among Allogeneic Hematopoietic Stem Cell Transplantation Patients

Association between CYP3A4, CYP3A5, and ABCB1 Genotype, Tacrolimus Concentrations, and Outcomes Among Allogeneic Hematopoietic Stem Cell Transplantation Patients

Age, Sex and Self-Reported Race Differences in Immune Profiles of Hematologic Malignancy Patients

Age, Sex and Self-Reported Race Differences in Immune Profiles of Hematologic Malignancy Patients

Social Vulnerability Is a Clinically Important Predictor of Outcomes after Allogeneic Hematopoietic Cell Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is an established treatment for malignant and non-malignant hematologic diseases. However, HCT is not without risk; rates of non-relapse mortality (NRM) remain high during the first year after transplantation. Clinical prediction models have been developed to identify those at increased risk for NRM after HCT, but the impact of social determinants of health on transplant outcomes has not been well characterized. To address this gap, we evaluated the relationship between census tract-level social vulnerability and 1y NRM following HCT. Methods: Using a retrospective cohort design, this study included 1,602 patients living in California (CA) who underwent a first allogeneic HCT between 2013-2019 at City of Hope. Demographic, insurance, disease, treatment, and survival information was abstracted from the medical records. Social vulnerability according to the census tract was measured using the Social Vulnerability Index (SVI), a tool developed by the Center for Disease Control. SVI comprises 4 themes (socioeconomic status [SES], household composition & disability, minority status & language, and housing & transportation) constructed using 15 social and environmental variables from the US Census. This study used the overall SVI and individual theme scores which were ranked across the CA census tracts as percentiles; the scores ranged from 0 (least vulnerable) to 100 (most vulnerable). Scores were assigned to patients using their address at the time of HCT. Fine-Gray multivariable regression was used to evaluate the association between SVI, tertiles of SVI, and 1y NRM, adjusted for age at HCT, performance status, relapse risk (RR), human leukocyte antigen (HLA) match, and HCT-Comorbidity Index (HCT-CI). We also performed subgroup analysis to examine the risk of NRM across combined SVI and HCT-CI categories: 1) lower two SVI tertiles (low social vulnerability) and low (<3) HCT-CI score (reference); 2) low social vulnerability and high (≥3) HCT-CI score; 3) high social vulnerability (upper SVI tertile) and low HCT-CI score; 4) high social vulnerability and high HCT-CI score. Results: Median age at HCT for the cohort was 52.0 years (IQR 33.0-63.0); 55.8% were male; 44.6% were non-Hispanic white; 59.1% had private insurance. The most common diagnosis was acute myeloid leukemia (40.7%) and 54.1% received reduced intensity conditioning. In the first year after HCT, 357 patients died (NRM 15.3% [n=245], relapse-related 7.0% [n=112]). In multivariable analysis, there was a significant linear relationship between worsening overall SVI and the risk of 1y NRM (SVI coefficient=0.0056, 95% confidence interval [CI]: 0.001-0.010, p=0.017). Patients in the highest SVI tertile (most socially vulnerable) had a 1.4-fold (HR=1.41, 95%CI: 1.08-1.83, p=0.011) risk of 1y NRM compared to those in the lowest two SVI tertiles. When the 4 themes were evaluated individually, increased risk for 1y NRM was found for the highest SVI tertiles for SES (HR=1.43, 95% CI: 1.10-1.86, p=0.008), household composition & disability (HR=1.32, 95% CI: 1.02-1.71, p=0.036), and minority status & language (HR=1.40, 95% CI: 1.08-1.83, p=0.013). When the themes were considered together in one regression model, only the highest SVI tertile for SES retained significance. The one-year cumulative incidence of 1y NRM was highest (22.0%) for patients who had both high social vulnerability and a high HCT-CI score at HCT (Figure 1); in adjusted analysis, patients who had both high social vulnerability and HCT-CI scores were at a 1.6-fold (HR=1.64, 95% CI: 1.21-2.24, p=0.002) risk of 1y NRM compared to the rest of the patients. Conclusion: Among allogeneic HCT recipients, SVI, especially within the theme of SES, was an independent predictor of 1y NRM, after adjusting for RR, performance status, age at HCT, HLA match, and HCT-CI score. Patients with both the highest social vulnerability and high comorbidity had particularly increased risk of 1y NRM, suggesting that in addition to clinical risk factors, local social and environmental factors play an important role in health outcomes following HCT. These findings may inform more targeted approaches for needs assessment during and shortly after HCT, allowing for timely interventions to improve health outcomes in at-risk allogeneic HCT patients. [Display omitted] DisclosuresArtz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Forman: Allogene: Consultancy; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company.

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed. We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations. We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition. Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.

Pediatric-inspired regimen with late intensification and increased dose of L-asparaginase for adult acute lymphoblastic leukemia: the KALLA 1406/1407 study.

Background/AimsThe objective of this study was to evaluate the efficacy and feasibility of the pediatric-inspired regimen of the adult acute lymphoblastic leukemia (ALL) Working Party, the Korean Society of Hematology.MethodsData of 99 patients with newly diagnosed ALL, who were treated with the KALLA 1406/1407 protocol, were retrospectively analyzed. All patients equally received age-adjusted daunorubicin, vincristine, and prednisolone. L-asparaginase was additionally administered to Philadelphia (Ph)-negative patients according to age, whereas Ph-positive patients received 600 mg/day of imatinib.ResultsA total of 99 patients were enrolled in this study, of whom 62 (62.6%) were diagnosed with Ph-negative ALL and 37 (37.3%) were diagnosed with Ph-positive ALL. The median age of patients in the Ph-negative ALL group was 46 years, and that of patients in the Ph-positive ALL group was 49 years. In patients with Ph-negative ALL, 57 (92%) patients achieved complete remission (CR) and CR with incomplete hematologic recovery (CRi). Disease-free survival (DFS) and overall survival (OS) rates at 2 years were estimated to be 42% and 63%, respectively. In patients with Ph-positive ALL, 32 (86%) patients achieved CR/CRi, and 2-year DFS and OS were 31.2% and 49.1%, respectively. Patients who were able to proceed to the allogeneic hematopoietic cell transplantation and younger patients showed significantly superior survival in both Ph-negative ALL and Ph-positive ALL. Neutropenic fever and bacterial infection were the most common and severe adverse events.ConclusionsThe KALLA 1406/1407 protocol showed tolerable toxicities in adult ALL patients. Especially, younger patients had more survival benefits with KALLA 1406/1407 protocol.

Association of Host Factors With Antibody Response to Seasonal Influenza Vaccination in Allogeneic Hematopoietic Stem Cell Transplant Patients.

BackgroundInfluenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood.MethodsWe investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison.ResultsBoth regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT patients can elicit potent antibody responses. However, an unrelated donor, absolute lymphocyte counts below the normal range, and treatment with calcineurin inhibitors lowered the odds of responding.ConclusionsHSCT patients show a highly heterogeneous vaccine response but, overall, patients benefited from the booster shot and can acquire seroprotective antibodies over the years after transplantation. Several common patient factors lower the odds of responding, urging identification of additional preventive strategies in the poorly responding groups.Clinical Trials RegistrationNCT03467074.