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Do all patients with primary refractory/first relapse of HL need autologous stem cell transplant?

ABSTRACT: The standard approach to treatment of primary refractory/first relapse of classical Hodgkin lymphoma (cHL) is administration of second-line therapy (SLT) followed by consolidation with high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). Historically, this approach cured about 50% of patients. Due to improvements in supportive care, positron emission tomography-adaptive strategies, and incorporation of novel agents into SLT, contemporary studies show that about 75% of patients with primary refractory or first relapse of cHL can be cured. Recent studies evaluating incorporation of PD-1 blockade in SLT appear to show even further improvement in remission rates and bring into question whether an aggressive approach that includes HDT/AHCT is needed for everyone. To address this question, several ongoing studies are beginning to explore the possibility of avoiding or delaying HDT/AHCT for patients with primary refractory or first relapse of cHL.

SUBMITTER: Moskowitz AJ

PROVIDER: S-EPMC9821042 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Do all patients with primary refractory/first relapse of HL need autologous stem cell transplant?

Moskowitz Alison J AJ

Hematology. American Society of Hematology. Education Program 20221201 1

The standard approach to treatment of primary refractory/first relapse of classical Hodgkin lymphoma (cHL) is administration of second-line therapy (SLT) followed by consolidation with high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). Historically, this approach cured about 50% of patients. Due to improvements in supportive care, positron emission tomography-adaptive strategies, and incorporation of novel agents into SLT, contemporary studies show that about 75% of ...[more]

PMID: 36485099

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Project description:ImportanceHematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.ObjectiveTo compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL.Data sourcesA systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020.Study selectionAfter duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantation-related mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Data extraction and synthesisData on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model.Main outcomes and measuresThe prespecified main outcomes were OS, PFS, and TRM.ResultsOf 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this meta-analysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed.Conclusions and relevanceIn this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.

Project description:BackgroundThe present study intended to establish a predictive nomogram for early relapse (ER) (<12 months) after autologous stem cell transplantation (ASCT) in the novel drug era for multiple myeloma (MM).Patients and methodsThe nomogram was designed and constructed to a retrospective clinical data of newly diagnosed MM patients received novel agent induction therapy and subsequent ASCT at three centers in China from July 2007 to December 2018. The retrospective study was conducted among 294 patients in the training cohort and 126 in the validation cohort. The nomogram's predictive accuracy was evaluated by the concordance index, calibration curve and decision clinical curve.ResultsThe study cohort included 420 newly diagnosed MM patients, and 100 (23.8%) were identified as having ER, including 74 in the training cohort and 26 in the validation cohort. According to the result of multivariate regression in the training cohort, the prognostic variables included in the nomogram were high-risk cytogenetics, LDH > UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C-index achieved 0.75 (95% CI, 0.70-0.80), which was higher than that of the Revised International Staging System (R-ISS) (0.62), ISS (0.59), and Durie-Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C-index: 0.73 vs. R-ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS.ConclusionThe present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation-eligible MM patients, which could help modify the post-ASCT strategy for patients at high risk of ER.

Project description:BackgroundThe prognosis of Hodgkin lymphoma (HL) relapsing post autologous transplant (AuSCT) is poor. Even with novel therapies, only approximately 20%-25% of patients attain complete remissions, with a median progression-free survival (PFS) of approximately 5-15 months. Lenalidomide has been shown to have activity in relapsed HL. We retrospectively analyzed the outcomes of patients with relapsed HL post AuSCT treated with lenalidomide alone or in combination with dexamethasone at our center.Patients and methodsRecords of 143 patients transplanted from November 2007 to October 2021 were reviewed. Of these patients, 41 (28%) relapsed, and 16 (39%) received lenalidomide alone or in combination with dexamethasone. Data collected included demographic, pathological, staging, and prior therapy details. Lenalidomide was administered at 10-25 mg/day on an intermittent or continuous schedule alone or in combination with dexamethasone (20-40 mg weekly). Response was assessed using PET-CT scan in accordance with Lugano criteria. Standard definitions were used for response, PFS, and overall survival (OS). Toxicities were graded using Common Terminology Criteria for Adverse Events version 5.0. Statistical analysis was done using SPSS Version 21.ResultsThe median age of the patients was 25.5 years, and 10 were males. Eleven (69%) had advanced disease, and 7 (44%) were refractory to last systemic therapy. Nine patients received lenalidomide alone and 7 with dexamethasone. Four (25%) had complete response, and another four (25%) had partial response, with an overall response rate of 50%. The 3-year PFS and OS were 31% and 38%, respectively. Grade III/IV toxicities were only hematological, neutropenia and thrombocytopenia in four and three patients, respectively. No therapy-related deaths were recorded.ConclusionsLenalidomide alone or in combination with dexamethasone is a safe and effective therapy for relapsed HL post AuSCT and results in durable response and long-term survival in approximately one-third of the patients. However, these results needs verification in larger prospective studies.

Project description:BackgroundHigh-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease.Patients and methodsEligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population.ResultsWe enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively.ConclusionsSequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.ClinicaltrialsgovNCT00936936.

Project description:BackgroundSecond allogeneic hematopoietic stem cell transplant (HCT) remains as an option for disease relapse after initial HCT.MethodsWe analyzed retrospectively the outcomes of 65 consecutive patients who underwent a second HCT for disease relapse at the University of Chicago. Univariate and multivariate analysis were conducted, and a scoring system was generated to select the patients who would benefit second HCT.ResultsAll except four patients received T cell depleted (TCD) first HCT. The majority of patients had AML (n = 47) and high risk MDS (n = 5). The median age at second HCT was 45 years (11-73). 13 patients (20%) achieved CR before second HCT. 98% (n = 64) and 72% (n = 47) patients achieved neutrophil and platelet engraftment at a median interval of 10 and 18 days, respectively, following the second HCT. With a median follow up of 23 (5.5-140) months for survivors after second HCT, the estimated 2 years PFS was 17.5% and the 2 years OS was 22.6%. The day 100 cumulative incidence of non-relapse mortality rate was 23.6%, and the cumulative incidence of aGVHD and cGVHD were 16.9% and 7.7% respectively at 1 year after second HCT. In univariate analysis, patients with remission duration after first HCT of > 12 months and those in CR before second HCT had significantly better PFS and OS. A scoring system using disease status before second HCT (CR = 0 vs. non-CR = 1), and remission duration after first HCT (< 6 = 2, 6-12 = 1 and > 12 months = 0) was generated as an approach to classify patients into different risk categories in the purpose to provide guidance to the transplant physician to inform the outcomes to potential patients undergoing 2nd HCT. A score of < 2 (n = 26) identified a group with PFS and OS of 31.6% and 36.2% at 2 years after second HCT.ConclusionIn conclusion, second HCT is a viable option for disease relapse after TCD HCT for patients entering second HCT in remission and/or remission duration > 12 months after first HCT with acceptable rates of GVHD and donor engraftment.

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Do all patients with primary refractory/first relapse of HL need autologous stem cell transplant?

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Do all patients with primary refractory/first relapse of HL need autologous stem cell transplant?

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