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1.
Blood Adv ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776400

RESUMEN

Socioeconomic status (SES) and race/ethnicity have been associated with outcomes of allogeneic hematopoietic cell transplantation (allo-HCT). Certain aspects of GVHD management such as the need for long term care, prolonged immunosuppressive treatment, and need for close follow up for complications may exacerbate disparities. Adults (≥ 18 years) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent a first alloHCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm between 2008 - 2018 were included. Endpoints for those developing GVHD included overall survival (OS), transplant related mortality (TRM), and disease relapse. Models were adjusted for patient and transplant related variables. A two-sided p-value < 0.01 was considered significant. Among the 14,825 allo-HCT recipients, 6,259 (42.2%) and 6,675 (45.0%) patients developed aGVHD and cGVHD, respectively. In patients with aGVHD, non-Hispanic Blacks had increased TRM (HR 1.50, 95% CI 1.24-1.83, p=0.0001) and overall mortality (HR 1.31, 1.14-1.50, p=0.0002) compared with non-Hispanic Whites, an association that disappeared when severity of aGVHD was included in the model. Lower SES was associated with increased risk of disease relapse (p=0.0016) but not OS or TRM. In patients who developed cGVHD, race and ethnicity were not associated with OS, TRM and disease relapse. However, the highest quartile of annual household income (≥ $80,000) had improved OS (HR 0.77, 0.69-0.85, p<0.0001) and reduced TRM (HR 0.86, 0.67-0.87, p<0.0001) compared with lowest quartile, adjusting for race and ethnicity. Race/ethnicity and SES are associated with outcomes after GVHD. Optimizing health care resources available to low SES patients and strategies to minimize the risk of severe GVHD in non-Hispanic Blacks may improve long-term outcomes.

2.
Blood Adv ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38661372

RESUMEN

There has been an increase in volume as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have impacted racial/ethnic minorities equally. In this observational study from Center for International Blood and Marrow Transplant Research of 79,904 autologous (auto) and 65,662 allogeneic (allo) HCTs, we examined the volume and rates of change of auto HCT and allo HCT over time and trends in OS in 4 racial/ethnic groups: Non-Hispanic Whites (NHWs), Non-Hispanic African Americans (NHAAs), Hispanics across five 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs. NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (HR 1.13; 95% CI 1.04-1.22; p=0.004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; p<0.001 had a higher risk of mortality after alloHCT compared to NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT.Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics compared to NHWs. Survival after autoHCT and alloHCT improved over time, however NHAAs have worse OS after alloHCT which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

3.
Bone Marrow Transplant ; 59(4): 459-465, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38238453

RESUMEN

Autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for eligible patients with multiple myeloma (MM) to prolong progression-free survival (PFS). While several factors affect survival following ASCT, the impact of social determinants of health such as the CDC Social Vulnerability Index (SVI) is not well documented. This single-center retrospective analysis evaluated the impact of SVI on PFS following ASCT in MM patients. 225 patients with MM who underwent ASCT participated, with 51% transplanted in the last 5 years. At 5 years post-transplant, 55 (50%) achieved PFS and 66 (60%) remained alive. Higher SVI values were significantly associated with lower odds of PFS (OR = 0.521, p < 0.01, 95% CI [0.41, 0.66]) and OS (OR = 0.592, p < 0.01, 95% CI [0.46, 0.76]) post-transplant. Greater vulnerability scores in the socioeconomic status (OR = 0.890; 95% CI: [0.82, 0.96]), household characteristics (OR = 0.912; 95% CI: [0.87, 0.95]), and racial and ethnic minority status (OR = 0.854; 95% CI: [0.81, 0.90]) themes significantly worsened the odds of PFS. These results suggest high SVI areas may need more resources to achieve optimal PFS and OS. Future studies will focus on addressing factors within the socioeconomic status, household characteristics, and racial and ethnic minority subthemes, as these have a more pronounced effect on PFS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Estudios Retrospectivos , Etnicidad , Vulnerabilidad Social , Grupos Minoritarios , Trasplante de Células Madre , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Autólogo , Supervivencia sin Enfermedad , Resultado del Tratamiento
4.
Blood Adv ; 7(22): 7007-7016, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37792849

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trastornos Mieloproliferativos , Humanos , Persona de Mediana Edad , Trasplante Homólogo , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Trastornos Mieloproliferativos/patología , Enfermedad Crónica , Recurrencia , Células Dendríticas/patología
5.
Transplant Cell Ther ; 29(11): 709.e1-709.e11, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37482244

RESUMEN

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Disparidades Socioeconómicas en Salud , Adulto , Humanos , Estados Unidos , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia , Enfermedad Crónica , Sobrevivientes
6.
Blood ; 142(15): 1271-1280, 2023 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-37352612

RESUMEN

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P < .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.


Asunto(s)
Anemia , Leucemia Linfocítica Granular Grande , Neutropenia , Ratones , Animales , Humanos , Citocinas/metabolismo , Leucemia Linfocítica Granular Grande/patología , Interleucina-15
7.
Haematologica ; 108(7): 1900-1908, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36779595

RESUMEN

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) and inferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan. Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Adulto , Humanos , Adolescente , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/terapia , Busulfano/uso terapéutico , Melfalán , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento Pretrasplante , Vidarabina/uso terapéutico
8.
Hematol Oncol Stem Cell Ther ; 16(1): 61-69, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36634280

RESUMEN

OBJECTIVE/BACKGROUND: Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic cell transplantation (HCT) occurring in approximately 60-70% of CMV-seropositive HCT recipients. CMV reactivation leads to adverse outcomes including end-organ damage, graft-versus-host disease, and graft failure. METHODS: Ganciclovir was administered pretransplant at 5 mg/kg twice daily intravenously from the start of conditioning to Day T-2 to CMV-seropositive patients receiving their first allogeneic HCT. CMV DNA was monitored weekly until at least Day 100 posttransplant. RESULTS: A total of 109 consecutive patients were treated, median age 57 (range 20-73) years. Of these, 36 (33%) patients had a CMV reactivation within the first 105 days posttransplant with a median time of reactivation of 52.5 (range 36-104) days posttransplant. The cumulative incidence of CMV reactivation at Day 105 posttransplant was 33.1% (95% confidence interval: 24.4-42.0). One patient developed CMV disease. CONCLUSION: The use of pretransplant ganciclovir was associated with low incidence of CMV reactivation and disease. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation may be a useful strategy to reduce CMV reactivation. Future prospective trials are needed to compare strategies for CMV prophylaxis.


Asunto(s)
Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Ganciclovir/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología
10.
Rheumatology (Oxford) ; 61(10): 4155-4162, 2022 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-35108379

RESUMEN

OBJECTIVES: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy. METHODS: Lymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization. RESULTS: Compared with healthy controls, individuals with SSc showed significant reductions in central memory CD8 T cells, activated total and CD4 T cells, γ/δ T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3+CD25+ Treg cells and increases in naïve CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4+ Th2/T cytotoxic 2 (Tc2) phenotype based on the Th2:Th1 CD4 ratio and Tc2:Tc1 CD8 T cells was also found. Notably, no difference in any lymphocyte subset was observed between those given or not given prior DMARDs. CONCLUSIONS: In patients with early, severe SSc, significant lymphocyte subset abnormalities were observed. Prior treatment with immunosuppressive therapy did not impact the immunophenotype, suggesting that lymphocyte disturbances in scleroderma appeared to be due to the disease itself. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT00114530.


Asunto(s)
Antirreumáticos , Células TH1 , Linfocitos T CD8-positivos , Ciclofosfamida/uso terapéutico , Factores de Transcripción Forkhead , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Interleucina-4 , Subgrupos Linfocitarios , Fenotipo , Subgrupos de Linfocitos T , Células Th2
11.
Front Oncol ; 12: 781479, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35223471

RESUMEN

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive hematologic malignancy with a poor prognosis. Alemtuzumab (Campath) remains the cornerstone for treatment, with an 80% complete response (CR). Hematopoietic stem cell transplant (HSCT) is considered the standard of care as consolidative therapy in eligible patients. However, allogeneic stem cell transplant is also complicated by increased rates of infections from chemotherapy, acute graft-versus-host disease (GVHD), and chronic GVHD. This review aims to report the available literature on the efficacy and complications of consolidative HSCT. It also discusses the importance of patient selection and pre- and post-transplant complications including atypical infections and GVHD.

12.
Leuk Lymphoma ; 63(6): 1428-1435, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35075985

RESUMEN

We sought to assess the safety of adding ixazomib, an oral proteasome inhibitor, to a multi-agent treatment regimen for older adults with acute lymphoblastic leukemia (ALL). Patients 51 to 75 years of age with newly diagnosed ALL were screened. Induction consisted of prednisone (P), vincristine (V), and doxorubicin (D). For BCR-ABL1+ patients, dasatinib was added. On Days 1, 8, 15 of induction, ixazomib was given orally. After induction patients received 1 cycle of consolidation in which ixazomib was given on Days 1, 8, 15. After consolidation, patients in remission (CR) were offered stem cell transplantation. Among the 19 patients treated, 15 (79%) [90% CI, 58-92%] achieved CR or CRi. At 2 years, the overall survival was 47% [95%CI, 29-72%]. In this study the dose of 2.3 mg of ixazomib in combination was the MTD for older patients with ALL and is the recommended dose for future phase 2 studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Boro/efectos adversos , Glicina/análogos & derivados , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Inducción de Remisión , Resultado del Tratamiento , Vincristina/uso terapéutico
13.
Blood Adv ; 6(1): 339-357, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34547770

RESUMEN

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sangre Fetal , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Hermanos , Donante no Emparentado
14.
Bone Marrow Transplant ; 56(11): 2864-2865, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34446854
15.
Transplant Cell Ther ; 27(11): 885-907, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34461278

RESUMEN

In 2021 the BMT CTN held the 4th State of the Science Symposium where the deliberations of 11 committees concerning major topics pertinent to a particular disease, modality, or complication of transplant, as well as two committees to consider clinical trial design and inclusion, diversity, and access as cross-cutting themes were reviewed. This article summarizes the individual committee reports and their recommendations on the highest priority questions in hematopoietic stem cell transplant and cell therapy to address in multicenter trials.


Asunto(s)
Trasplante de Médula Ósea , Trasplantes , Ensayos Clínicos como Asunto , Trasplante de Células Madre Hematopoyéticas , Humanos
16.
Blood Adv ; 5(20): 4064-4072, 2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34461630

RESUMEN

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as an important treatment modality. Most reports comparing haplo-HSCT with posttransplant cyclophosphamide (PTCy) and other donor sources have focused on outcomes in older adults treated with reduced intensity conditioning. Therefore, in the current study, we evaluated outcomes in patients with hematological malignancy treated with myeloablative conditioning prior to haplo- (n = 375) or umbilical cord blood (UCB; n = 333) HSCT. All haplo recipients received a 4 of 8 HLA-matched graft, whereas recipients of UCB were matched at 6-8/8 (n = 145) or ≤5/8 (n = 188) HLA antigens. Recipients of 6-8/8 UCB transplants were younger (14 years vs 21 and 29 years) and more likely to have lower comorbidity scores compared with recipients of ≤5/8 UCB and haplo-HSCT (81% vs 69% and 63%, respectively). UCB recipients were more likely to have acute lymphoblastic leukemia and transplanted in second complete remission (CR), whereas haplo-HSCT recipients were more likely to have acute myeloid leukemia in the first CR. Other characteristics, including cytogenetic risk, were similar. Survival at 3 years was similar for the donor sources (66% haplo- and 61% after ≤5/8 and 58% after 6-8/8 UCB). Notably, relapse at 3 years was lower in recipients of ≤5/8 UCB (21%, P = .03) compared with haplo- (36%) and 6-8/8 UCB (30%). However, nonrelapse mortality was higher in ≤5/8 UCB (21%) compared with other groups (P < .0001). These data suggest that haplo-HSCT with PTCy after myeloablative conditioning provides an overall survival outcome comparable to that after UCB regardless HLA match group.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Anciano , Neoplasias Hematológicas/terapia , Humanos , Acondicionamiento Pretrasplante
17.
Transplant Cell Ther ; 27(10): 837.e1-837.e10, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34224914

RESUMEN

The incidence of debilitating oral mucositis (OM) can be as high as 99% after myeloablative conditioning regimens preparing patients with hematologic malignancies for hematopoietic cell transplantation (HCT). Palifermin (KGF) is a recombinant human keratinocyte growth factor that reduces the incidence and duration of severe OM. The long-term safety of KGF has not been well established, however. In this long-term prospective matched-cohort study, patients who received KGF (cases) and underwent autologous or allogeneic HCT for hematologic malignancies between 2006 and 2013 were matched 1:1 to patients who did not receive KGF (controls). The primary outcome was overall survival (OS). Other outcomes were disease relapse, new malignancies, pancreatitis, renal failure requiring dialysis, pulmonary complications, cataract surgery, and acute and chronic graft-versus-host disease (GVHD). The analysis population comprised 2191 matched pairs with a wide range of diseases and donor types that received diverse conditioning and GVHD preventive regimens, representing contemporary practice patterns. The median duration of follow-up was 8 years (range, 1 to 12.5 years). In multivariate analyses, the probabilities of OS (relative risk [RR], 1.01; 95% confidence interval [CI], 0.91 to 1.12), relapse (RR, 1.06; 95% CI, 0.94 to 1.18), new malignancies (RR, 0.89; 95% CI, 0.67 to 1.18), and cataract surgery (RR, 1.05; 95% CI, 0.74 to 1.50) were not statistically significantly different between cases and controls. In univariate analyses, no increased risks were observed for renal failure requiring dialysis, pancreatitis, acute GVHD, chronic GVHD, interstitial pneumonitis/acute respiratory distress syndrome/idiopathic pneumonia syndrome, or bronchiolitis obliterans/cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia among cases compared with controls. This long-term prospective safety cohort study demonstrates that the KGF group had no increased risk of overall mortality, relapse, new malignancies, or any other key outcome. The broad inclusion criteria allow the results to be generalized to contemporary practice for patients with a wide range of diseases and receiving a wide range of HCT conditioning regimens and graft sources from diverse donor types.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Estudios de Cohortes , Factor 7 de Crecimiento de Fibroblastos/uso terapéutico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Recurrencia Local de Neoplasia , Estudios Prospectivos
18.
Transplant Cell Ther ; 27(10): 869.e1-869.e9, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34224915

RESUMEN

Allogeneic hematopoietic cell transplantation (HCT) is a standard therapy for patients with intermediate to high-risk acute myeloid leukemia (AML) and is associated with improved long-term disease-free survival. Disparity exists in access to HCT among different patient populations and requires further study. In this study, we compared HCT rates for AML among different regions in the state of Virginia and identified geographic and socioeconomic factors associated with the likelihood of receiving HCT. We conducted a retrospective, cohort study of patients 18 to 74 years of age diagnosed with AML in Virginia from 2013 to 2017 as reported to the Virginia Cancer Registry (VCR); the VCR was further linked with the Center for International Blood and Marrow Transplant Research database for identification of patients who had undergone HCT within 2 years of diagnosis. Socioeconomic data were generated from the VCR and the American Community Survey. Univariate and multivariable logistic regression models were used to examine selected socioeconomic factors of interest, including patient-level information such as sex, age, race, marital status, and primary insurance payer, as well as factors associated with geography, including the Social Vulnerability Index (SVI) and percentage of African Americans residing in the region. In Virginia, 818 patients were diagnosed with AML from 2013 to 2017, and, of these, 168 patients (21%) underwent HCT within 2 years of diagnosis. Median age was lower in the HCT cohort (55 years) versus the non-HCT cohort (64 years) (P < .001). There was a higher proportion of married patients in the HCT cohort (67%) versus the non-HCT cohort (53%) (P = .005). The rate of HCT varied by geographic region (P = .004). The multivariable analyses (without including SVI) showed decreased likelihood of HCT with increasing age (odds ratio [OR], .96; 95% confidence interval [CI], .95 to .98). Patients from regions that had a greater than 25% African American population were less likely to undergo HCT (OR, .58; 95% CI, .38 to .89). Patients who were not married were less likely to undergo HCT compared with married patients (OR, .56; 95% CI, .36 to .88). Patients with government-sponsored insurance as the primary payer were less likely to undergo HCT compared with patients with private insurance (OR, .49; 95% CI, .32 to .77). Patients living in Zip Code areas with a greater percentage of population with a bachelor's or graduate degree were more likely to undergo HCT (OR, 1.02; 95% CI, 1.00 to 1.03). In a separate multivariate model with SVI, patients residing in a Zip Code with higher SVI were less likely to undergo HCT (OR, .37; 95% CI, .16 to .82). From 2013 to 2017, we found that the likelihood of a patient undergoing HCT in Virginia for AML within 2 years of diagnosis was negatively associated with increasing age, percent of African Americans residing in the region, not-married relationship status, government-sponsored insurance as primary payer, higher SVI, and decreased percent of population with a bachelor's or graduate degree. Resources should be directed toward at-risk patient populations to remove barriers to improve access to HCT. The SVI can be used to identify communities at risk nationwide.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Preescolar , Estudios de Cohortes , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Virginia/epidemiología
20.
Transplant Cell Ther ; 27(4): 286-291, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33836867

RESUMEN

For cord blood transplantation (CBT), appropriate patient and conditioning regimen selection is necessary to achieve long-term disease-free survival. This review aims to provide comprehensive guidelines on these issues using evidence from the literature and experience at dedicated CBT centers. Topics include patient and disease characteristics that make CBT a good or poor choice and a review of outcomes in commonly used conditioning regimens in CBT. This is accompanied with recommendations on regimen intensity based on disease, organ function, and patient performance status and age. In addition, the use of antithymocyte globulin in CBT is discussed, as is the choice of conditioning in aplastic anemia patients who have access to acceptable CB units.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas , Adulto , Anemia Aplásica/terapia , Neoplasias Hematológicas/terapia , Humanos , Selección de Paciente , Acondicionamiento Pretrasplante
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