Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 360
Filtrar
1.
Transplant Cell Ther ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844022

RESUMO

BACKGROUND: Post-transplant cyclophosphamide (PTCy) is a safe and efficacious graft-versus-host-disease (GvHD) prophylaxis following hematopoietic cell transplantation (HCT) from haploidentical (haplo) donors. Cytokine release syndrome (CRS) is a common complication of this platform. Early fever post-haplo HCT using bone marrow grafts is associated with higher CD3+ cell dose and CRS. However, the impact of CD3+ and CD34+ cell dose on CRS post-haplo HCT using peripheral blood stem cell (PBSCT) grafts is unknown. OBJECTIVE: Our goals were to evaluate the incidence of CRS following PBSCT and to identify factors that can be modified to prevent the development of severe CRS in this setting. STUDY DESIGN: In 271 patients, we investigated factors associated with development of CRS following haplo PBSCT and examined the impact of CRS on clinical outcomes. RESULTS: Ninety-three percent of patients developed CRS of any grade post-haplo PBSCT. In multivariate analysis, severe CRS (grade 3-4 vs. grade 0-1) was associated with higher non-relapse mortality (HR=6.42; 95% CI: 2.68-15.39; p<0.001), worse 1-year overall survival (HR=3.40; 95% CI: 1.63-7.08; p=0.005), and disease-free survival (HR=4.02, 95% CI: 1.99-8.08; p<0.001). Moderate to severe CRS (grade 2-4) did not impact 1-year relapse and acute GvHD (grade II-IV and III-IV) at 100 days (p=0.71 and p=0.19, respectively). Importantly, higher CD3+ cell dose but not CD34+ cell dose predicted higher incidence of CRS grades 2-4 (HR=1.20, 95% CI:1.07-1.36; p 0.003) and grades 3-4 (HR=1.40, 95% CI:1.05-1.86; p=0.022). Older age (HR=8.57, 95% CI: 1.73-42.36; p<0.001) and non-radiation-based RIC (fludarabine/melphalan; HR=15.38, 955 CI: 2.06-114.67; p<0.001) were both predictors of CRS grade 3-4. CONCLUSIONS: Overall, we observed that severe CRS (grade 3-4) negatively affected transplant outcome and that higher CD3 cell dose was associated with development of any grade and severe CRS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34802049

RESUMO

Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) as graft-versus-host disease (GvHD) prophylaxis post-hematopoietic cell transplantation (HCT) is safe and effective. Optimal serum levels of TAC in this combination remain undetermined. We hypothesized that TAC at initial steady state (TISS) of <10 ng/mL could promote optimal transplant outcomes and prevent TAC-associated toxicities. We retrospectively analyzed a consecutive case series of 210 patients who received PTCy/TAC-based prophylaxis post-HCT from 1/2013-6/2018. Patients received HCT from haploidentical (n = 172) or mismatched donors (n = 38), and flat dose (FD) or weight-based dose (WBD) TAC. Twenty-four-month overall survival (OS), disease free survival (DFS), and relapse rate (RR) were 61%, 56%, and 22%, respectively, in TISS < 10 ng/mL cohort (n = 176), and 50%, 43%, and 35%, respectively, in TISS ≥ 10 ng/mL cohort (n = 34) (OS, P = 0.71; DFS, P = 0.097; RR, P = 0.031). OS, DFS, RR, non-relapse mortality, acute GvHD grade II-IV, grade III-IV or chronic GvHD by TISS were similar in multivariable analysis. TISS ≥ 10 ng/mL conferred increased risk of viral infection (P = 0.003). More patients receiving FD vs. WBD had TISS < 10 ng/mL (P = 0.001). Overall, TISS < 10 ng/mL early post HCT conferred similar survival outcomes and lowered risk of viral infection and toxicities compared to TISS ≥ 10 ng/mL.

3.
Blood Adv ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34638132

RESUMO

High-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL and we hypothesized that the addition of 90Y-antiCD25 (aTac) to BEAM AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled onto this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution and a third developed an unrelated catheter-associated bacteremia; therefore 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed and 0.6mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive > 2500cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with 3 or more risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL and we are further evaluating the efficacy of this approach in a phase 2 trial. The clinical trial was registered at clinicaltrials.gov (NCT01476839).

4.
Cancer ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633671

RESUMO

BACKGROUND: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19- disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. METHODS: This study retrospectively reviewed the outcomes of adult patients with B-cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013-2021) and analyzed factors associated with treatment response and EMD failure. RESULTS: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. CONCLUSIONS: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure. LAY SUMMARY: Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites. Most extramedullary failure cases retain CD19 expression.

5.
Leuk Lymphoma ; 62(12): 2823-2830, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34713775

RESUMO

Allogeneic hematopoietic cell transplantation (alloHCT) is a curative option for the treatment of eligible patients with hematological malignancies. This modality confers a risk for life-threatening complications, including the rare and underdiagnosed complication of donor-derived leukemia (DDL). DDL differs from relapse of the original malignancy in that DDL originates from the donor stem cells and is unrelated to the original diagnosis. Because DDL may be the same lineage as the original diagnosis, it is difficult to identify these cases and many remain unrecognized. There is no consensus of how to approach the treatment of patients with DDL, and their prognosis is poor considering that patients with DDL have already been treated for their original leukemia and have undergone alloHCT. DDL occurs following transplants using any donor stem cell source (bone marrow, peripheral blood and cord blood) and any donor type (matched/unmatched, related/unrelated and haploidentical). Both donor and recipient factors contribute to the development of DDL, and a better understanding of these factors is crucial to reduce the risk for the development of DDL. In this review, we provide an overview of DDL, including the incidence, diagnosis, etiology, prognosis, and treatment.

6.
Clin Cancer Res ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675084

RESUMO

Immunotherapy has failed to achieve durable remissions in advanced prostate cancer patients. More potent T-cell-redirecting strategies may be needed to overcome the immunologically exclusive and suppressive tumor microenvironment. Clinical trials are underway, seeking to define the optimal target for T-cell redirection, such as PSMA, PSCA, or STEAP-1, as well as the optimal strategy, with CAR or bispecific antibodies. As results continue to emerge from these trials, understanding differential toxicity and efficacy of these therapies based on their targets and functional modifications will be key to advancing these promising therapies toward clinical practice. This review provides a unique depth and breadth of perspective regarding the diverse immunotherapy strategies currently under clinical investigation for men with advanced prostate cancer.

7.
JAMA Oncol ; 7(11): 1626-1634, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34499078

RESUMO

Importance: The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival. Objective: To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period. Design, Setting, and Participants: A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020. Exposures: Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014. Main Outcomes and Measures: All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases. Results: Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend). Conclusions and Relevance: This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.

8.
Int J Hematol ; 114(5): 544-553, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34561840

RESUMO

Adoptive transfer of in vitro expanded, chimeric antigen receptor (CAR)-redirected CD19-specific T cells can induce dramatic disease regression in patients with leukemia and lymphomas. However, the full potential of this emerging modality is hampered in some cancer settings by a significant rate of therapeutic failure arising from the attenuated engraftment and persistence of CAR-redirected T cells, and tumor relapse following adoptive transfer. Here, we discuss an advanced strategy that facilitates post-infusion in vivo boosting of CAR T cells via CMV vaccination, to mediate durable remission of B cell malignancies by engrafting a CAR molecule onto a CMV-specific T cell. We also discuss a feasible and unique platform for the generation of the CMV-CD19CAR T cells for clinical application. This new approach would overcome multiple challenges in current CAR T cell technology including: short T cell persistence, limited duration of response, and inability to re-stimulate T cells after relapse or persistent disease.

9.
Blood Adv ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581764

RESUMO

We report results of our prospective pilot trial (NCT02917096) evaluating safety/feasibility of peri-transplant administration of ruxolitinib for myelofibrosis treatment. Primary objectives were to determine the safety and identify maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was given at two dose levels (DL) of 5 and 10mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus GVHD prophylaxis. We enrolled 6 and 12 patients in DL-1 and DL-2, respectively. Median age at transplant was 65 years (range:25-73) for all patients. Per DIPSS, 4 patients were at high and 14 were at intermediate risk. PBSCs was the graft source from a matched sibling (n=5) or unrelated (n=13) donor. At each DL one patient developed DLTs: Grade 3 cardiac and GI with Grade 4 pulmonary in DL-1 and Grade 3 kidney injury in DL-2. All patients achieved engraftment. Cumulative incidence (CI) of acute GVHD grade 2-4 and 3-4 were 17% (95% CI: 6-47) and 11% (95% CI: 3-41), respectively. CI of 1-year chronic GVHD was 42% (95% CI: 24-74). With the median follow-up of 22.6 months (range:6.2-25.8) in surviving patients the 1-year overall and progression free survival were 77% (95% CI: 50-91) and 71% (95% CI: 44-87), respectively. Causes of death (n=4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results showed that peri-HCT ruxolitinib was safe and well-tolerated with the MTD determined as 10 mg BID, associated with dose-dependent PK and cytokine profile. The early efficacy data are highly promising in this group of high-risk older patients with MF.

10.
Front Immunol ; 12: 700045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539628

RESUMO

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.

11.
Blood Adv ; 5(20): 4031-4043, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34474478

RESUMO

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.


Assuntos
Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Doadores de Tecidos , Transplante Homólogo
12.
Blood Adv ; 5(20): 4059-4063, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34492703

RESUMO

CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity. Here, we report the outcome of a subset of patients with primary CNS lymphoma (PCNSL; n = 5) who were treated with CD19CAR T cells in our ongoing phase 1 clinical trial. All patients developed grade ≥ 1 cytokine release syndrome and neurotoxicity post-CAR T-cell infusion; toxicities were reversible and tolerable, and there were no treatment-related deaths. At initial disease response, 3 of 5 patients (60%; 90% confidence interval, 19-92%) seemed to achieve complete remission, as indicated by resolution of enhancing brain lesions; the remaining 2 patients had stable disease. Although the study cohort was small, we demonstrate that using CD19CAR T cells to treat PCNSL can be safe and feasible. This trial was registered at www.clinicaltrials.gov as #NCT02153580.


Assuntos
Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Antígenos CD19 , Humanos , Imunoterapia Adotiva , Linfoma não Hodgkin/terapia , Linfócitos T
13.
Blood Adv ; 5(20): 4102-4111, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34461633

RESUMO

Allogeneic blood or marrow transplant (BMT) recipients are at risk for venous thromboembolism (VTE) because of high-intensity therapeutic exposures, comorbidities, and a proinflammatory state due to chronic graft-versus-host disease (GVHD). The long-term risk of VTE in allogeneic BMT survivors remains unstudied. Participants were drawn from the Blood or Marrow Transplant Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived ≥2 years after BMT. We analyzed the risk of VTE in 1554 2-year survivors of allogeneic BMT compared with 907 siblings. Using backward variable selection guided by minimizing Akaike information criterion, we created a prediction model for risk of late-occurring VTE. Allogeneic BMT survivors had a 7.3-fold higher risk of VTE compared with siblings (95% CI, 4.69-11.46; P < .0001). After a median follow-up of 11 years, conditional on surviving the first 2 years after BMT, the cumulative incidence of late-occurring VTE was 2.4% at 5 years, 4.9% at 10 years, and 7.1% at 20 years after BMT. The final model for VTE risk at 2 years post-BMT included History of stroke, chronic GVHD, Hypertension, Sex (male vs female) and Stem cell source (peripheral blood stem cells vs other) ("HiGHS2") (corrected C-statistics: 0.73; 95% CI = 0.67-0.79). This model was able to classify patients at high and low VTE risk (10-year cumulative incidence, 9.3% vs 2.4% respectively; P < .0001). The BMTSS HiGHS2 risk model when applied at 2 years post-BMT can be used to inform targeted prevention strategies for patients at high risk for late-occurring VTE.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tromboembolia Venosa , Medula Óssea , Transplante de Medula Óssea/efeitos adversos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sobreviventes , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
15.
Transplant Cell Ther ; 27(11): 938.e1-938.e6, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34274492

RESUMO

The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) emergency-use authorized (EUA) vaccines have been confirmed in the general population. However, there are no data on its safety and tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines, the incidence of new-onset graft-versus-host disease (GVHD) or worsening of existing GVHD after EUA vaccine administration, and the incidence SARS-CoV2 positivity in vaccinated HCT patients. We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety and tolerability, any impact on GVHD, and the incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and had received at least one dose of vaccine in the post-HCT setting. Most patients presented with myalgias/arthralgias (first dose, 7.7%; second dose, 14.6%), fatigue (first dose, 15.4%; second dose, 29.2%), and injection site pain (first dose, 40.4%; second dose, 43.8%). Other side-effects experienced by patients included nausea, vomiting, diarrhea, headache, and injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. Neutropenia, thrombocytopenia, and lymphopenia occurred in 13.3%, 11.5%, and 8.8% of patients, respectively. Forty percent of patients had active chronic GVHD at the time of vaccination, and worsening chronic GVHD occurred in 3.5% of the patients. New chronic GVHD developed in 9.7% of patients after vaccination. The SARS-CoV2 EUA vaccines were well tolerated in allogeneic HCT recipients.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Vacinas , Vacinas contra COVID-19 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , RNA Viral , Estudos Retrospectivos , SARS-CoV-2
16.
Transplant Cell Ther ; 27(10): 840.e1-840.e7, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34153501

RESUMO

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent-based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR]2000-2005 = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR2006-2014 = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR2000-2005 = 0.50, 95% CI, 0.29-0.85; SHR2006-2014 = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR2000-2005 = 0.45, 95% CI 0.20-0.99; SHR2006-2014 = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years.


Assuntos
Mieloma Múltiplo , Transplante de Células-Tronco de Sangue Periférico , Medula Óssea , Humanos , Mieloma Múltiplo/terapia , Estudos Prospectivos , Sobreviventes , Transplante Autólogo
17.
Bone Marrow Transplant ; 56(10): 2464-2470, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34108676

RESUMO

Currently, there is no consensus on best practices to prevent hemorrhagic cystitis (HC) in patients receiving posttransplant cyclophosphamide (PTCy). We retrospectively reviewed 194 patients undergoing their first hematopoietic cell transplant (HCT) who received PTCy from 2014 to 2018 to describe the incidence and severity of HC, identify potential risk factors, and impact of HC on HCT outcomes. Standard HC prophylaxis was hyperhydration with forced diuresis and mesna at 320% the daily dose of PTCy. Incidence of HC was 31.4% at day +100 of HCT. Median onset of HC was 12 days with 11.5% grade 3 HC and no Grade 4 HC. Patients with chemical HC experienced earlier onset (7 days vs. 34 days, p < 0.001) with a shorter median resolution time (5 days vs. 14 days, p = 0.001) when compared to BK-associated HC. In multivariate analysis, age above 60 years (HR 4.16, p = 0.006) and myeloablative conditioning (HR 2.44, p = 0.054) were associated with higher risk for HC, but overall, HC did not affect nonrelapse mortality or overall survival. In conclusion, hyperhydration with forced diuresis combined with aggressive mesna dosing is an effective strategy in preventing severe PTCy-associated HC, subsequently preventing any negative impact on transplant outcome.


Assuntos
Cistite , Transplante de Células-Tronco Hematopoéticas , Ciclofosfamida/efeitos adversos , Cistite/epidemiologia , Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Mesna/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo
18.
Blood Adv ; 5(12): 2650-2659, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34156440

RESUMO

Efficacy of PTCy after mismatched unrelated donor (MMUD) HCT is unknown. In this pilot clinical trial, we enrolled 38 patients with hematologic malignancies scheduled to undergo MMUD-HCT (≥6/8 HLA-matched donors) onto 1 of 2 conditioning strata: myeloablative using fludarabine and fractionated total body irradiation (n = 19) or reduced intensity with fludarabine/melphalan (n = 19). Graft source was peripheral blood stem cells (PBSCs), and GVHD prophylaxis was PTCy, tacrolimus, and mycophenolate mofetil. Patients' median age was 53 years (range, 21-72 years). Median number of HLA mismatches was 2 (range, 1-4) of 12 loci. Twenty-three patients (61%) were considered racial (n = 12) or ethnic (n = 11) minorities. Median time to neutrophil engraftment was 16 days (range, 13-35 days). With a median follow-up of 18.3 months (range, 4.3-25.0 months) for surviving patients, 1-year overall survival (OS) and GVHD-free/relapse-free survival (GRFS) were 87% (95% confidence interval [CI]: 71-94) and 68% (95% CI: 51-81), respectively. Cumulative incidence of nonrelapse mortality at 100 days and 1 year were 0% and 11% (95% CI: 4-27), respectively, whereas relapse/progression was 11% (95% CI: 4-27). Cumulative incidence of 100-day acute GVHD grades 2-4 and 3-4 and 1-year chronic GVHD were 50% (95% CI: 36-69), 18% (95% CI: 9-36), and 48% (95% CI: 34-68), respectively. The rate of moderate/severe chronic GVHD was 3% in the entire cohort. We showed highly promising OS/GRFS rates with an acceptable risk profile after PBSC-MMUD-HCT with PTCy. This trial was registered at www.clinicaltrials.gov as #NCT03128359.


Assuntos
Doença Enxerto-Hospedeiro , Células-Tronco de Sangue Periférico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Doadores não Relacionados
19.
J Clin Oncol ; 39(30): 3328-3339, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34106753

RESUMO

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined. METHODS: We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration. RESULTS: The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm (P = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; P = .003). The survival benefit was seen across all subgroups examined. CONCLUSION: We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...