Allogeneic hematopoietic cell transplantation for patients with TP53 mutant or deleted chronic lymphocytic leukemia: Results of a prospective observational study.
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ABSTRACT:
SUBMITTER: Schetelig J
PROVIDER: S-EPMC8589674 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Allogeneic hematopoietic cell transplantation (alloHCT) can cure previously treated high-risk chronic lymphocytic leukemia (CLL) patients if they are suitable for transplant through the graft-versus-leukemia effect. However, since the emergence of targeted therapies, the role of alloHCT for high-risk CLL is less clear. To address this question, we evaluated 108 high-risk CLL patients who underwent alloHCT from 2010 to 2018. Thirty patients from the period of 2013 to 2018 received targeted therapy prior to alloHCT. The median age for the targeted therapy cohort was 60 years (range, 30-71 years), and 20% and 73% had complete and partial remission, respectively: 76% had del(17p), 46.2% had 5 or more cytogenetic abnormalities, and 78.9% were IGHV unmutated. The median number of prior therapies was 4 (range, 1-9). With a median follow-up time of 36 months (range, 10-72 months), the 3-year overall (OS) and progression-free survival (PFS) were 87% and 69%, respectively. The 3-year cumulative incidence of nonrelapse mortality and relapse was 7% and 24%, respectively. For the control cohort of 78 patients who underwent alloHCT from 2010 to 2014 and received only chemoimmunotherapy prior to transplant, the 3-year OS and PFS were 69% and 58%, respectively. Patients treated with targeted therapy prior to alloHCT had a significantly higher number of circulating T and B cells and a lower ratio of CD4 regulatory T cells to CD4 conventional T cells early after transplant. In summary, despite multiple high-risk features, the clinical outcome of CLL patients who receive targeted therapy prior to transplant is excellent and alloHCT should be offered while the disease is under control.
| S-EPMC7479951 | biostudies-literature
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| S-EPMC6518913 | biostudies-literature
Project description:Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.
| S-EPMC5944847 | biostudies-literature
Project description:Allogeneic blood or marrow transplantation (allo-BMT) remains the only treatment for chronic lymphocytic leukemia (CLL) with curative potential. Although post-transplantation cyclophosphamide (PTCy) reduces allo-BMT toxicity by decreasing the risk of graft-versus-host disease (GVHD), its effect on CLL allo-BMT outcomes is unknown. We studied 64 consecutive patients with CLL who underwent nonmyeloablative (NMA) haploidentical allo-BMT at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. In this cohort, the 4-year overall survival was 52% (95% confidence interval [CI], 40% to 68%), and progression-free survival was 37% (95% CI, 26% to 54%). Six patients experienced engraftment failure. PTCy prophylaxis was associated with a modest cumulative incidence of 1-year grade II-IV acute GVHD (27%; %95% CI, 15% to 38%) and %%%2-year chronic GVHD (17%; 95% CI, 7% to 26%). We demonstrate that NMA haploidentical allo-BMT with PTCy is a safe and effective treatment option.
| S-EPMC9353745 | biostudies-literature
Project description:In acute leukemia, advances have been made in therapeutic strategies centered on allogeneic hematopoietic stem cell transplantation (allo-SCT), three of which are presented here. The indication of allo-SCT for acute myeloid leukemia (AML) in 1st complete remission (CR1) has been debated. Genomic medicine has helped us gain a deeper understanding of this disease, some of which may serve as prognostic factors. Such genetic abnormalities could also help measure minimal residual disease (MRD) and provide additional clues to estimate the efficacy of chemotherapy. Combined with existing prognostic factors, these data can be used to construct a more accurate prognostic model, providing an optimal indication of allo-SCT for AML in CR1. Furthermore, overall treatment algorithms for high-risk AML after allo-SCT should include prophylactic and pre-emptive treatment to prevent relapse. These include immunotherapy using donor lymphocyte infusion (DLI), FLT3 inhibitors in FLT3-mutated AML, hypomethylating agents, or a combination of DLI with these agents. Clinical trials are currently ongoing to elucidate the role of these strategies, which will lead to a risk-adapted treatment for preventing relapse in high-risk AML. CD19-targeted chimeric antigen receptor (CAR) T-cell therapy induces a remarkable response in B-acute lymphoid leukemia (B-ALL); however, relapse remains a major problem. In this regard, allo-SCT as a consolidation treatment after CAR-T cell therapy for B-ALL is recommended for pediatric and adult patients. Achieving complete remission (CR) with CAR-T cell therapy is considered a promising bridging therapy to allo-SCT. Novel CAR-T treatment techniques are being developed to change their role as a pre-transplant treatment.
| S-EPMC10200363 | biostudies-literature
Project description:BackgroundAllogeneic stem cell transplantation (allo-HSCT) is the ultimate cure for acute lymphoblastic leukemia (ALL).AimThis study was performed to compare the outcomes of ALL patients receiving busulfan (Bu) with cyclophosphamide (Cy)-based or total body irradiation (TBI)-based regimen in a Chinese population.MethodsWe enrolled 224 adult patients with ALL who received allo-HSCT at National Taiwan University Hospital between 1997 and 2016.ResultsThe median age at transplantation was 33 years. Before allo-HSCT, 75.9% of patients attained first or late complete remission. A total of 141 patients (62.9%) received Bu/Cy-based conditioning, either myeloablative (MA) or reduced-intensity stem cell transplantation (RIST), and 83 patients received a TBI-based regimen (MA-TBI). Patients receiving the MA-Bu regimen had longer relapse-free survival (RFS) than those receiving the MA-TBI regimen (median, 24.1 vs. 6.7 months, p = .044). There was no difference in overall survival (OS, MA-Bu vs. MA-TBI vs. RIST-Bu: 39.4 vs. 28.2 vs. 13.1 months, p = .276), treatment-related mortality (TRM), or incidences of grade 3-4 acute graft-versus-host disease (GvHD). Among patients receiving identical GvHD prophylactic regimens, there was no difference between MA-Bu and MA-TBI groups regarding the incidence of grade 3-4 acute GvHD, grade 2-4, and all-grade chronic GvHD. In subgroup analysis, patients receiving oral busulfan had comparable RFS and OS to the intravenous busulfan group (p = .436 and p = .236, respectively), but a higher TRM (25% vs. 9.8%, p = .016). In the multivariable analysis, disease status before allo-HSCT was the only risk factor impacting RFS and OS.ConclusionIn summary, patients receiving Bu/Cy-based or TBI-based regimens as conditioning had similar results in terms of OS, TRM, and acute GvHD, whereas the use of myeloablative Bu/Cy resulted in a better RFS. A Bu-based regimen could be an alternative conditioning choice for patients who are ineligible to receive TBI. Prospective and randomized controlled trials are warranted to validate the long-term outcomes.
| S-EPMC8955073 | biostudies-literature
Project description:In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide therapy. Five (62%) patients had to stop taking the drug because of toxicity. The main reason for drug discontinuation was acute GVHD in 43% of patients. This incidence was 11% in the patients who were randomized to not receive lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4 years for those receiving lenalidomide. This was not reached in patients randomized to not receive lenalidomide and in patients in complete remission who were not randomized. These results suggested that treatments other than lenalidomide are needed for persistent CLL after alloSCT.
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Project description:Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (<20 years), but no significant differences were observed between those 20 to 40 years of age and those who were 40 years or older. A matched-pair analysis showed similar outcomes comparing MPAL cases to 375 acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival.
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Project description:Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P?=?.021), age >35 years (HR, 1.55; P?=?.025), and disease status at HCT (HR, 1.98; P?=?.005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.
| S-EPMC5549947 | biostudies-literature
Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for many children with high-risk or relapsed acute leukemia (AL), thanks to the combination of intense preparative radio/chemotherapy and the graft-versus-leukemia (GvL) effect. Over the years, progress in high-resolution donor typing, choice of conditioning regimen, graft-versus-host disease (GvHD) prophylaxis and supportive care measures have continuously improved overall transplant outcome, and recent successes using alternative donors have extended the potential application of allotransplantation to most patients. In addition, the importance of minimal residual disease (MRD) before and after transplantation is being increasingly clarified and MRD-directed interventions may be employed to further ameliorate leukemia-free survival after allogeneic HSCT. These advances have occurred in parallel with continuous refinements in chemotherapy protocols and the development of targeted therapies, which may redefine the indications for HSCT in the coming years. This review discusses the role of HSCT in childhood AL by analysing transplant indications in both acute lymphoblastic and acute myeloid leukemia, together with current and most promising strategies to further improve transplant outcome, including optimization of conditioning regimen and MRD-directed interventions.
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