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Risk factors predicting graft-versus-host disease and relapse-free survival after allogeneic hematopoietic stem cell transplantation in relapsed or refractory non-Hodgkin's lymphoma.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still considered a definitive curative modality for refractory or relapsed non-Hodgkin's lymphoma (NHL). However, transplant-related morbidity and mortality remain a considerable challenge. The graft-versus-host disease (GVHD)-free with relapse-free survival (GRFS) rate and GRFS-related prognostic factors have not been fully examined for NHL alone. We evaluated 104 consecutive patients with refractory or relapsed aggressive NHL receiving allo-HSCT at a single institution. With a median follow-up of 31.5 months, the estimated 3-year overall survival (OS), disease-free survival (DFS), the cumulative incidence rates of relapse, and non-relapse mortality were 45.9%, 45.9%, 36.0%, and 17.0%, respectively. The patients with overall grades III-IV acute GVHD had markedly inferior OS and DFS (p?=?0.040 for OS and p?=?0.028 for DFS). However, patients with more than mild stage chronic GVHD showed superior OS and DFS (p?=?0.004 and p?=?0.008, respectively). The 1- and 3-year GRFS rates were 44.5% and 36.9%, respectively. The negative bone marrow involvement at diagnosis, chemosensitive disease status, and fewer exposure lines of chemotherapy before transplantation significantly increased the GRFS incidence. However, no transplant-associated factors were related to GRFS incidence. Furthermore, applying dynamic GRFS method which excepted patients whose chronic GVHD was fully resolved within short-period, survival rate significantly increased over time (36.9% vs. 41.9%, p?=?0.045 for conventional GRFS vs. dynamic GRFS at 3 years after transplantation). In conclusion, these results suggest that GRFS is also a useful endpoint to assess transplant outcomes, and the dynamic GRFS calculation, including rapidly manageable chronic GVHD, is a more practical method for patients with refractory or relapsed heterogenous subtypes of NHL.

SUBMITTER: Jeon YW

PROVIDER: S-EPMC6591200 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Risk factors predicting graft-versus-host disease and relapse-free survival after allogeneic hematopoietic stem cell transplantation in relapsed or refractory non-Hodgkin's lymphoma.

Jeon Young-Woo YW Yoon Seugyun S Min Gi June GJ Park Sung-Soo SS Park Silvia S Yoon Jae-Ho JH Lee Sung-Eun SE Cho Byung-Sik BS Eom Ki-Seong KS Kim Yoo-Jin YJ Kim Hee-Je HJ Lee Seok S Min Chang-Ki CK Lee Jong Wook JW Cho Seok-Goo SG

Annals of hematology 20190514 7

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still considered a definitive curative modality for refractory or relapsed non-Hodgkin's lymphoma (NHL). However, transplant-related morbidity and mortality remain a considerable challenge. The graft-versus-host disease (GVHD)-free with relapse-free survival (GRFS) rate and GRFS-related prognostic factors have not been fully examined for NHL alone. We evaluated 104 consecutive patients with refractory or relapsed aggressive NHL re ...[more]

PMID: 31089793

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Project description:Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma.In this ongoing study, 23 patients with relapsed or refractory Hodgkin's lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression.Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed-Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling.Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT01592370.).

Dataset Information

Risk factors predicting graft-versus-host disease and relapse-free survival after allogeneic hematopoietic stem cell transplantation in relapsed or refractory non-Hodgkin's lymphoma.

Publications

Risk factors predicting graft-versus-host disease and relapse-free survival after allogeneic hematopoietic stem cell transplantation in relapsed or refractory non-Hodgkin's lymphoma.

Similar Datasets

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