RESUMO
Acute and chronic graft-versus-host disease (GvHD) are major complications of allogeneic hematopoietic cell transplantation (alloHCT). In vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG) as part of the conditioning regimen prior to alloHCT is frequently used as GvHD prophylaxis, but data on its role in myelofibrosis is scarce. We took advantage of an international collaborative network to investigate the impact of ATLG in myelofibrosis undergoing first alloHCT. We included 707 patients (n = 469 ATLG and n = 238 non-ATLG prophylaxis). The cumulative incidence of acute GvHD grade II-IV was 30% for the ATLG group vs. 56% for the non-ATLG group (P < 0.001). Acute GvHD grade III-IV occurred in 20% vs. 25%, respectively (P = 0.01). Incidence of mild-to-severe chronic GvHD was 49% vs. 50% (P = 0.52), while ATLG showed significantly lower rates of severe chronic GvHD (7% vs. 18%; P = 0.04). GvHD-free and relapse-free survival (GRFS) at 6 years was 45% for the ATLG group vs. 37% for the non-ATLG group (P = 0.02), driven by significantly improved GRFS of ATLG in matched related and matched unrelated donors. No significant differences in risk for relapse, non-relapse mortality, and overall survival were observed. Multivariable modeling for GRFS showed a 48% reduced risk of GvHD, relapse, or death when using ATLG.
Assuntos
Soro Antilinfocitário , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Doadores não Relacionados , Humanos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Mielofibrose Primária/terapia , Mielofibrose Primária/mortalidade , Soro Antilinfocitário/uso terapêutico , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Intervalo Livre de Doença , Condicionamento Pré-Transplante/métodos , Aloenxertos , Adulto JovemRESUMO
ABSTRACT: Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130.
Assuntos
Alemtuzumab , Ciclosporina , Doença Enxerto-Hospedeiro , Imunossupressores , Metotrexato , Sirolimo , Tacrolimo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Alemtuzumab/uso terapêutico , Alemtuzumab/administração & dosagem , Doença Crônica/prevenção & controle , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversosRESUMO
While curing a patient's underlying disease is the primary goal of physicians performing hematopoietic cell transplantation (HCT), the ultimate objective is to provide patients with optimal post-HCT quality of life. For many survivors, this includes returning to work (RTW). We conducted a survey of 1- to 5-yr post-HCT survivors at our center to evaluate their perspective on facilitators and barriers to RTW as well as to gauge interest in potentially useful RTW support interventions. Survivors aged 18 to 65 yrs (n = 994) were sent an annual survey that included 36 supplementary questions about post-HCT RTW. Survey questions were selected from published national cancer survivor surveys and then modified specifically for HCT survivors. Three hundred forty-four (35%) survivors with a mean age of 53 yrs completed the survey, of whom 272 (79%) had worked prior to their diagnosis. Of those 272 patients, 145 (53%) were working currently and another 22 (8%) had attempted to go back to work following HCT but were not presently working. We found that having had an allogeneic versus autologous HCT (P = .006) was associated with a decreased likelihood of currently working, whereas frequent employer communication (>once a month) (P = .070) and having a more supportive employer (P = .036) were associated with a greater chance of currently working. Of survivors currently working, 45% reported that they had made one or more changes to their work schedule (e.g., flexible schedule or part-time work) or environment (e.g., work from home) upon RTW. Ninety-five percent of responders reported that they could have benefited from RTW support provided by the transplant center, but only 13% indicated that they had received it. Education on RTW challenges, information on disability benefits, and access to physical therapy were among the most requested support interventions. To improve post-HCT quality of life for survivors open to assistance, providers should address work status and goals, recognize barriers to successful return, and offer RTW support including working directly with employers. Allogeneic HCT survivors are particularly vulnerable to failing attempts to RTW and should be the target of retention interventions. A previously published manuscript on RTW guidance for providers of stem cell transplant patients endorsed by the American Society of Transplant and Cellular Therapy is available in Open Access and can be used as a tool to counsel and support these patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Qualidade de Vida , Retorno ao Trabalho , Sobreviventes , Humanos , Transplante de Células-Tronco Hematopoéticas/psicologia , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Retorno ao Trabalho/estatística & dados numéricos , Idoso , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Patients with multiple myeloma (MM) may be on therapy for years, which can lead to financial toxicity (FinTox) or time toxicity (TimeTox). The prevalence, predictors, and quality of life (QOL) impacts of FinTox and TimeTox during different phases of MM treatment have not been characterized. PATIENTS AND METHODS: We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. FinTox+ was defined as a COST-FACIT score <23, TimeTox+ as MM-related interactions (including phone calls) ≥1x weekly or ≥1x monthly in-person among far-residing patients, QOL using PROMIS Global Health, and functional status using patient-reported Karnofsky performance status (KPS). RESULTS: Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ predictors included annual income (P < .01) and out-of-pocket costs (P < .01). TimeTox+ predictors included disease status (P < .001), caregiver status (P = .01), far-residing status (P < .001), and out-of-pocket costs (P = .03). FinTox+ was associated with a clinically meaningful decrease in mental QOL, while TimeTox+ patients were more likely to have KPS ≤ 80. CONCLUSIONS: In our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. FinTox+ was associated with decreased mental health, while TimeTox+ was associated with worse performance status. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development.
Assuntos
Mieloma Múltiplo , Qualidade de Vida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , AdultoRESUMO
New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Mielofibrose Primária/terapia , Esplenomegalia , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/métodos , Baço , Condicionamento Pré-TransplanteRESUMO
TP53 mutations (TP53MTs) have been associated with poor outcomes in various hematologic malignancies, but no data exist regarding its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MT in this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multihit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of patients with TP53MT was 1.5 vs 13.5 years for those with wild-type TP53 (TP53WT; P < .001). Outcome was driven by multihit TP53MT constellation (P < .001), showing 6-year survival of 56% for individuals with single-hit vs 25% for those with multihit TP53MT vs 64% for those with TP53WT. Outcome was independent of current transplantation-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multihit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P < .001). Out of the 10 patients with TP53MT, 8 showed multihit constellation. Median time to leukemic transformation was shorter for multihit and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multihit TP53MT represents a very high-risk group in patients with myelofibrosis who are undergoing HSCT, whereas single-hit TP53MT alone showed similar outcome to patients with nonmutated TP53, informing prognostication for survival and relapse together with current transplantation-specific tools.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Mielofibrose Primária/complicações , Doença Enxerto-Hospedeiro/etiologia , Transplante Homólogo/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Doença Crônica , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genéticaRESUMO
With improved survival after hematopoietic cell transplantation (HCT), the number of individuals at risk for persistent or late effects is increasing. The importance of optimizing HCT survivor health and well-being is mounting. Fatigue is a common post-transplantation symptom that impairs quality of life, yet it remains poorly understood and inadequately addressed. Multiple challenges to addressing fatigue exist, including its multidimensional presentation, multiple (often concomitant) causes, patient-clinician communication barriers, and few highly effective, evidence-based interventions that can be readily implemented. To address these challenges, we sought to better describe the impact and potential causes of fatigue in the post-transplantation setting, fatigue-related communication with clinicians, and the most effective patient-identified mitigation strategies (PIMS) for fatigue. A total of 1703 adult HCT recipients from a single center completed a survey including the Medical Outcomes Survey Short Form-36 (SF-36), PROMIS Fatigue, and other fatigue-related items between July 2017-June 2018. The survey was offered to recipients at their post-transplantation anniversary occurring during this interval. Two independent raters categorized free-text responses about fatigue PIMS. PROMIS Fatigue scores were dichotomized into low (≤55) or high (>55). Associations between high fatigue and participant characteristics and health outcomes were evaluated using the Fisher exact test for categorical variables and the Student 2-sample t test for continuous variables. Among the 1660 respondents with evaluable fatigue scores, 67% underwent allogeneic HCT. The majority of these (n = 1588; 96%) had a malignancy, with hematologic malignancy the most common diagnostic category (n = 1555; 94%). The median time post-transplantation was 11 years (interquartile range, 4 to 20 years). PROMIS item responses indicate that 44% of patients were at least somewhat fatigued and 37% were at least somewhat bothered by it. The mean fatigue score was 50.2 ± 11; 591 patients (36%) had high fatigue, which was associated with worse SF-36 scores across all domains (General Health, Physical Functioning, Emotional Well-being/Mental Health, Social Functioning, Role Limitation due to Physical Health, Role Limitation due to Emotional Health, Vitality [eg, energy], and Bodily Pain). High fatigue also was associated with self-reported chronic graft-versus-host disease, anxiety, depression and sleep problems. Diagnosis of plasma cell disorder and receipt of an autologous transplant were associated with high fatigue (P = .001). Among the 553 individuals who received an autologous transplant, 226 (41%) had multiple myeloma. Compared with the autologous transplant recipients without myeloma group, those with multiple myeloma were significantly more likely to have high fatigue (109 of 226 [48%] versus 118 of 325 [36%]; P < .01). Twenty percent of the patients with high fatigue did not discuss it with their care team. Among the 89 different reasons provided for not discussing it, the most common was "thought they already knew the answer" (n = 21). The 370 survivors with high fatigue who identified at least 1 most effective PIMS generated a total of 639 PIMS. Although the PIMS for fatigue spanned a wide array of strategies, most PIMS were related to sleep/rest (n = 192; 30%) or exercise (n = 139; 22%). Although fatigue is associated with worse HCT survivor-reported outcomes, it is only sometimes discussed with care teams. Survivors identify specific strategies that are most effective. Given its prevalence and impact, clinicians should promote communication about fatigue, treat underlying causes, and recommend sleep/rest and exercise, recognizing that individualized approaches also may be beneficial.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Humanos , Qualidade de Vida , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/métodos , Sobreviventes/psicologia , Fadiga , Comunicação , Equipe de Assistência ao PacienteRESUMO
There is no direct evidence to recommend specific conditioning intensities in myelofibrosis undergoing allogeneic hematopoietic cell transplantation, especially in the molecular era. We aimed to compare outcomes of reduced intensity (RIC) or myeloablative conditioning (MAC) transplantation in myelofibrosis with molecular information. The study included 645 genetically annotated patients (with at least driver mutation status available), of whom 414 received RIC and 231 patients received MAC. The median follow-up time from transplantation was 6.0 years for RIC and 9.4 years for MAC. The 6-year overall survival rates for RIC and MAC were 63% (95% confidence interval [CI], 58%-68%) and 59% (95% CI, 52%-66%; P = 0.34) and progression-free survival was 52% (95% CI, 47%-57%) and 52% (95% CI, 45%-59%; P = 0.64). The 2-year cumulative incidence of nonrelapse mortality was 26% (95% CI, 21%-31%) for RIC and 29% (95% CI, 23%-34%) for MAC (P = 0.51). In terms of progression/relapse, the 2-year cumulative incidence was 10% (95% CI, 5%-19%) for RIC and 9% (95% CI, 4%-14%) for MAC (P = 0.46). Higher intensity conditioning did not seem to improve outcomes for higher-risk disease, according to mutational, cytogenetic, and clinical profile. In contrast, patients with reduced performance status, matched unrelated donors, and ASXL1 mutations appeared to benefit from RIC in terms of overall survival.
RESUMO
Hematopoietic cell transplantation (HCT) health care providers report a desire to improve long-term outcomes and quality of life for their patients. One of the items frequently cited by patients in terms of transitioning from being a patient back to pre-HCT life is return to work (RTW). However, these patients report little support from their health care providers in facilitating this process, and only 50% to 60% achieve RTW, at a median of 3 years post-HCT. Barriers are physical, psychological, and logistical, as well as poor communication between the patient and their employer. We convened a group of experts in survivorship, rehabilitation, social work, and psychology to draft an evidence-based document to assist health care providers in guiding their patients' RTW journey. Guidance is drawn from the existing literature for HCT and general cancer patients and is divided into pre-HCT, peri-HCT, and post-HCT categories. Collaboration among health care providers, patients, and their employers is key to this transition. Suggested referrals and evaluations also are provided. The goal is for this guidance to be continually updated as we advance the field with more HCT-specific literature.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Retorno ao Trabalho , Humanos , Estados Unidos , Retorno ao Trabalho/psicologia , Qualidade de Vida , Pessoal de Saúde , SobrevivênciaRESUMO
Although autologous and allogeneic hematopoietic cell transplantation are used to treat hematologic diseases, they are associated with high morbidity and mortality. The goal of this cross-sectional study was to describe the incidence, characteristics, severity and clinical correlates of neuropathy and muscle cramps, as self-reported by hematopoietic cell transplantation survivors. We included all respondents to a survey conducted July 1, 2020, to June 30, 2021. Surveys were completed online or on-paper according to participants' preferences; they received one reminder if no survey was received 1 month after distribution. Statistics are primarily descriptive comparing subgroups of patients. Of 4641 potentially eligible patients, 1745 responded and are included in the analysis. Participants (615 [35%] autologous, 1130 [65%] allogeneic) were a median age of 64.1 years (interquartile range [IQR] 55.2-70.8) and surveyed at a median of 11 years (IQR 4-21) after their most recent transplantation. Neuropathy symptoms were reported by 65% of autologous recipients, 66% of allogeneic transplant recipients with current chronic graft versus host disease (GVHD), and 45% of allogeneic recipients who never developed chronic GVHD. Muscle cramps were reported by 56% of autologous recipients, and 52% of allogeneic recipients and were rated as "very painful" by nearly half of patients who experienced them. These results suggest that neuropathy symptoms and muscle cramps are much more prevalent among survivors after hematopoietic cell transplantation than previously recognized. Better approaches for prevention and treatment of these bothersome complications are needed.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Idoso , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Cãibra Muscular , Sobreviventes , Transplante HomólogoRESUMO
The Janus Kinase (JAK)/Signal Transducers and Activators of Transcription (STAT) pathway is essential for both the regulation of hematopoiesis and the control of inflammation. Disruption of this pathway can lead to inflammatory and malignant disease processes. JAK inhibitors, designed to control the downstream effects of pro-inflammatory and pro-angiogenic cytokines, have been successfully used in pre-clinical models and clinical studies of patients with autoimmune diseases, hematologic malignancies, and the hematopoietic cell transplantation (HCT) complication graft versus host disease (GVHD). In the last decade, JAK inhibitors Ruxolitinib, Fedratinib, and most recently Pacritinib have been United States Federal Drug Administration (FDA) approved for the treatment of myelofibrosis (MF). Ruxolitinib was also recently approved for the treatment of steroid refractory acute as well as chronic GVHD; JAK inhibitors are currently under evaluation in the pre-HCT setting in MF and for the prevention of GVHD. This review will focus on the role of JAK inhibitors in the treatment of hematologic malignancies, the potential function of pre-HCT JAK inhibitors in patients with MF, and the role of JAK inhibitors in the prevention and treatment of acute and chronic GVHD.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Inibidores de Janus Quinases , Mielofibrose Primária , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológicoRESUMO
Accelerated-phase myelofibrosis, currently defined by circulating blasts 10% to 19%, usually confers very high risk for progression and poor outcome. The outcome of hematopoietic stem cell transplantation for accelerated-phase myelofibrosis has not been evaluated yet. We analyzed the outcome of 349 clinically and genetically annotated patients with primary or secondary myelofibrosis undergoing reduced intensity transplantation, of whom 35 had accelerated-phase myelofibrosis. In comparison with chronic-phase (<10% blasts) myelofibrosis, median leukocyte counts were higher, more patients had constitutional symptoms, and RAS mutations were detected more frequently in the accelerated-phase group. After a median follow-up of 5.9 years, estimated 5-year overall survival was 65% (95% confidence interval [CI], 49% to 81%) vs 64% (95% CI, 59% to 69%) for the chronic-phase group (P = .91), and median overall survival was not reached. In terms of relapse-free survival, estimated 5-year outcome for the accelerated-phase group was 49% (95% CI, 32% to 67%) vs 55% (95% CI, 50% to 61%) for the chronic-phase group (P = .65). Estimated 5-year nonrelapse mortality was 20% (95% CI, 8% to 33%) for the accelerated-phase group vs 30% (95% CI, 24% to 35%; P = .25) for the chronic-phase group. In terms of relapse, 5-year incidence was 30% (95% CI, 14% to 46%) for the accelerated-phase group vs 15% (95% CI, 11% to 19%) for the chronic-phase group (P = .02). Results were confirmed in multivariable analysis and propensity score matching. In conclusion, reduced intensity transplantation showed excellent survival but higher relapse for accelerated-phase myelofibrosis.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Doença Crônica , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Mielofibrose Primária/complicações , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Recidiva , Condicionamento Pré-Transplante/métodosRESUMO
Multiple studies have documented that racial/ethnic minority patients are less likely to undergo hematopoietic cell transplantation (HCT) in the United States (US), and if they do, they often have worse outcomes. No studies to our knowledge have compared the outcomes of English-speakers to non-English speakers undergoing HCT in the US. To test our hypothesis that non-English speakers have worse outcomes than English speakers after HCT, all transplants performed between 2015 and 2019 at Fred Hutchinson Cancer Research Center in Seattle, WA, USA were analyzed. Cox proportional hazards models were used to test our hypothesis, adjusting for significant clinical covariates. Out of 2051 patients, 106 (5%) were documented to be non-English speakers. Mortality for non-English speakers was not different than English speakers (adjusted HR 1.02, 95% CI 0.63-1.63, p = 0.95). When the analysis was limited to the allogeneic population, the results were similar to the total population (adjusted HR 1.10, 0.64-1.88, p = 0.73). The risk of grade II-IV acute graft-versus-host disease (GVHD) was higher in the non-English speaking subset: adjusted OR 2.01, 95% CI, 1.02-3.98, p = 0.04. These data suggest that non-English speakers have similar survival compared to English speakers following HCT although they have more acute GVHD.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Etnicidade , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Grupos Minoritários , Modelos de Riscos Proporcionais , Condicionamento Pré-Transplante/métodos , Estados UnidosRESUMO
Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Retorno ao Trabalho , Feminino , Humanos , Recidiva Local de Neoplasia , Sobreviventes , Transplante Homólogo , Estados Unidos , Adulto JovemRESUMO
The inclusion of mutation status improved risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML). Stem cell transplantation is a potentially curative treatment option, and patient selection is critical because of relevant transplant-related morbidity and mortality. We aimed to evaluate the impact of mutation status together with clinical presentations on posttransplant outcome. Our study included 240 patients with a median follow-up of 5.5 years. A significant association with worse survival was identified for the presence of mutations in ASXL1 and/or NRAS. In multivariable analysis, ASXL1- and/or NRAS-mutated genotype (hazard ratio [HR], 1.63), marrow blasts >2% (HR, 1.70), and increasing comorbidity index (continuous HR, 1.16) were independently associated with worse survival. A prognostic score (CMML transplant score) was developed, and the following points were assigned: 4 points for an ASXL1- and/or NRAS-mutated genotype or blasts >2% and 1 point each for an increase of 1 in the comorbidity index. The CMML transplant score (range, 0-20) was predictive of survival and nonrelapse mortality (P < .001 for both). Up to 5 risk groups were identified, showing 5-year survival of 81% for a score of 0 to 1, 49% for a score of 2 to 4, 43% for a score of 5 to 7, 31% for a score of 8 to 10, and 19% for a score >10. The score retained performance after validation (concordance index, 0.68) and good accuracy after calibration. Predictions were superior compared with existing scores designed for the nontransplant setting, which resulted in significant risk reclassification. This CMML transplant score, which incorporated mutation and clinical information, was prognostic in patients specifically undergoing transplantation and may facilitate personalized counseling.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/terapia , Mutação , Prognóstico , Transplante de Células-TroncoRESUMO
BACKGROUND: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown. METHODS: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ. RESULTS: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ. CONCLUSIONS: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Antivirais/uso terapêutico , Sangue Fetal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/epidemiologia , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Humanos , Incidência , Estudos RetrospectivosRESUMO
There is a limited understanding of the clinical and molecular factors associated with outcomes of hematopoietic cell transplantation (HCT) in patients with BCR-ABL-negative myeloproliferative neoplasms in blast phase (MPN-BP). Using the Center for International Blood and Marrow Transplant Research database, we evaluated HCT outcomes in 177 patients with MPN-BP. Ninety-five (54%) had sufficient DNA for targeted next-generation sequencing of 49 genes clinically relevant in hematologic malignancies. At 5 years, overall survival (OS), cumulative incidence of relapse, and nonrelapse mortality of the study cohort was 18%, 61%, and 25%, respectively. In a multivariable model, poor-risk cytogenetics was associated with inferior OS (hazard ratio [HR], 1.71; 95% CI, 1.21-2.41) due to increased relapse (HR, 1.93; 95% CI, 1.32-2.82). Transplants using mobilized peripheral blood (PB) were associated with better OS (HR, 0.60; 95% CI, 0.38-0.96). No difference in outcomes was observed in patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Among the 95 patients with molecular data, mutation of TP53, present in 23%, was the only genetic alteration associated with outcomes. In a multivariate model, TP53-mutant patients had inferior OS (HR, 1.99; 95% CI, 1.14-3.49) and increased incidence of relapse (HR, 2.59; 95% CI, 1.41-4.74). There were no differences in the spectrum of gene mutations, number of mutations, or variant allele frequency between patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Genetic factors, namely cytogenetic alterations and TP53 mutation status, rather than degree of cytoreduction predict outcomes of HCT in MPN-BP. No meaningful benefit of conventional HCT was observed in patients with MPN-BP and mutated TP53.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Crise Blástica/genética , Crise Blástica/terapia , Humanos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
We investigated risk factors for the development of mixed chimerism in 131 patients who underwent transplantation for myelofibrosis and determined the impact of lymphoid (CD3+) and myeloid (CD33+) chimerism on transplant outcome. Disease risk included DIPSS plus categories low to high. The median patient age was 58 years. Patients were conditioned with high-intensity (myeloablative) or low/reduced-intensity (nonmyeloablative) regimens and received a transplant from a related or unrelated donor. Mixed CD3+ chimerism was observed earlier after HCT, whereas CD33+ chimerism occurred later. Mixed chimerism was more frequent with low-intensity regimens than with high- intensity regimens. Mixed CD3+ chimerism did not lead to graft failure and was associated with a reduced incidence of acute GVHD and improved overall survival (OS) and relapse-free survival, whereas mixed CD33+ chimerism was associated with an increased incidence of relapse and reduced OS and relapse-free survival, independent of the CD34+ cell dose transplanted. Thus, mixed CD3+ chimerism in patients with myelofibrosis had a favorable impact on transplantation outcome and does not require therapeutic interventions.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Quimerismo , Doença Enxerto-Hospedeiro/etiologia , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/terapia , Quimeras de Transplante , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.
Assuntos
Doença Enxerto-Hospedeiro , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Sangue Fetal , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Hematopoietic cell transplantation (HCT) requires absence from work, with potential consequences of unemployment and early retirement. Risk factors for failure to return to work (RTW) following HCT have been reported, but there is little information about how transplant centers facilitate the RTW transition for their post-HCT patients. In the present study, we aimed to determine (1) whether transplant centers have guidelines for RTW post-HCT and the consistency of these guidelines and (2) whether centers have RTW programs for their patients, and the characteristics of these programs. We surveyed representatives from 150 adult transplant centers regarding their RTW guidelines and RTW programs. Centers were selected if they performed at least 50 HCTs (autologous [auto] and/or allogeneic [allo]) annually. The online survey contained 32 open-ended and closed-ended questions and 3 questions each eliciting respondents' demographic and transplant centers information. We received completed surveys from 45 centers (30% response rate). Forty-four percent of centers reported having RTW guidelines. All centers recommend RTW at 6 months or less after HCT for their auto-HCT recipients; recommendations for allo-HCT recipients ranged from 4 months to >1 year after HCT having jobs involving interactions with children, sick people, and animals was considered a reason to delay RTW by most centers. Although 87% of centers endorsed that RTW is a problem for post-HCT recipients, only 36% reported having an RTW program for their patients. The majority validated that RTW programs would be either somewhat helpful (36%) or very helpful (51%) for their patients. The majority of responding HCT centers believe that RTW is a problem for patients after HCT; however, consistent guidelines and RTW programs are lacking. With increasing numbers of HCT survivors, efforts to create standardized guidelines and to develop RTW programs are needed.