Allogeneic hematopoietic cell transplantation involves consideration of both donor and recipient characteristics to guide the selection of a suitable graft. Sufficient high-resolution donor–recipient ...HLA match is of primary importance in transplantation with adult unrelated donors, using conventional graft-versus-host disease prophylaxis. In cord blood transplantation, optimal unit selection requires consideration of unit quality, cell dose and HLA-match. In this summary, the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research, jointly with the NMDP Histocompatibility Advisory Group, provide evidence-based guidelines for optimal selection of unrelated donors and cord blood units.
Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > ...38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT.
We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy.
Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS.
Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the ...same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL).
Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day -19 and therapeutic dose of 0.75 Gy on day -12), carmustine 300 mg/m(2) (day -6), etoposide 100 mg/m(2) twice daily (days -5 to -2), cytarabine 100 mg/m(2) twice daily (days -5 to -2), and melphalan 140 mg/m(2) (day -1; B-BEAM) or rituximab 375 mg/m(2) on days -19 and -12 and the same chemotherapy regimen (R-BEAM).
Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001).
The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.
To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma.
Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not ...otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes.
AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio HR, 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival.
These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology.
Survivorship Care Plans (SCPs) may facilitate long-term care for cancer survivors, but their effectiveness has not been established in hematopoietic cell transplantation recipients. We evaluated the ...impact of individualized SCPs on patient-reported outcomes among transplant survivors. Adult (≥18 years at transplant) survivors who were 1-5 years post transplantation, proficient in English, and without relapse or secondary cancers were eligible for this multicenter randomized trial. SCPs were developed based on risk-factors and treatment exposures using patient data routinely submitted by transplant centers to the Center for International Blood and Marrow Transplant Research and published guidelines for long-term follow up of transplant survivors. Phone surveys assessing patient-reported outcomes were conducted at baseline and at 6 months. The primary end point was confidence in survivorship information, and secondary end points included cancer and treatment distress, knowledge of transplant exposures, health care utilization, and health-related quality of life. Of 495 patients enrolled, 458 completed a baseline survey and were randomized (care plan=231, standard care=227); 200 (87%) and 199 (88%) completed the 6-month assessments, respectively. Patients' characteristics were similar in the two arms. Participants on the care plan arm reported significantly lower distress scores at 6 months and an increase in the Mental Component Summary quality of life score assessed by the Short Form 12 (SF-12) instrument. No effect was observed on the end point of confidence in survivorship information or other secondary outcomes. Provision of individualized SCPs generated using registry data was associated with reduced distress and improved mental domain of quality of life among 1-5 year hematopoietic cell transplantation survivors. Trial registered at
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Background
Despite its established benefits, palliative care (PC) is rarely utilized for hematopoietic stem cell transplant (HSCT) patients. We sought to examine transplant physicians’ perceptions of ...PC.
Methods
We conducted a cross‐sectional survey of transplant physicians recruited from the American‐Society‐for‐Blood‐and‐Marrow‐Transplantation. Using a 28‐item questionnaire adapted from prior studies, we examined physicians’ access to PC services, and perceptions of PC. We computed a composite score of physicians’ attitudes about PC (mean = 16.9, SD = 3.37) and explored predictors of attitudes using a linear mixed model.
Results
277/1005 (28%) of eligible physicians completed the questionnaire. The majority (76%) stated that they trust PC clinicians to care for their patients, but 40% felt that PC clinicians do not have enough understanding to counsel HSCT patients about their treatments. Most endorsed that when patients hear the term PC, they feel scared (82%) and anxious (76%). Nearly half (46%) reported that the service name ‘palliative care’ is a barrier to utilization. Female sex (β = 0.85, P = .024), having <10 years of clinical practice (β = 1.39, P = .004), and perceived quality of PC services (β = 0.60, P < .001) were all associated with a more positive attitude towards PC. Physicians with a higher sense of ownership over their patients’ PC issues (β = ‐0.36, P < .001) were more likely to have a negative attitude towards PC.
Conclusions
The majority of transplant physicians trust PC, but have substantial concerns about PC clinicians’ knowledge about HSCT and patients’ perception of the term ‘palliative care’. Interventions are needed to promote collaboration, improve perceptions, and enhance integration of PC for HSCT recipients.
The majority of transplant physicians trust palliative care but have substantial concerns about palliative care clinicians’ knowledge about hematopoietic stem cell transplantation and patients’ perceptions of the term palliative care. Interventions are needed to promote collaboration, improve perceptions, and enhance the integration of palliative care for recipients of hematopoietic stem cell transplantation.
We ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT ...between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval CI, 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio OR = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age.
To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) ...versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course.
In all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients.
Auto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT.
For patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.
Patients who undergo human leukocyte antigen-matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often ...develop acute graft-versus-host disease (GVHD) despite standard calcineurin inhibitor-based prophylaxis in combination with methotrexate. This trial evaluated a novel human CD24 fusion protein (CD24Fc/MK-7110) that selectively targets and mitigates inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning. This phase 2a, multicenter study evaluated the pharmacokinetics, safety, and efficacy of CD24Fc in combination with tacrolimus and methotrexate in preventing acute GVHD in adults undergoing MUD HSCT for hematologic malignancies. A double-blind, placebo-controlled, dose-escalation phase to identify a recommended dose was followed by an open-label expansion phase with matched controls to further evaluate the efficacy and safety of CD24Fc in preventing acute GVHD. A multidose regimen of CD24Fc produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens. Grade 3 to 4 acute GVHD-free survival at day 180 was 96.2% (95% confidence interval CI, 75.7-99.4) in the CD24Fc expansion cohort (CD24Fc multidose), compared with 73.6% (95% CI, 63.2-81.4) in matched controls (hazard ratio, 0.1 95% CI, 0.0-0.6; log-rank test, P = .03). No participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD-free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as #NCT02663622.
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