Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis

Rashidi, Armin; Ebadi, Maryam; Cashen, Amanda F.

doi:10.1038/bmt.2015.332

Cited by 71 publications

(49 citation statements)

References 48 publications

(16 reference statements)

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“…[1][2][3][4] However, acute graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. 2 Despite standard immunosuppressive prophylaxis, acute GVHD develops in 50% to 70% of the patients receiving allogeneic HCT from unrelated donors (URDs), [5][6][7][8][9][10][11] and GVHD accounts for 13% to 16% of the mortality in this type of HCT.…”

Section: Introductionmentioning

confidence: 99%

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

Choi

Braun

Henig

et al. 2017

Blood

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Key Points• Grade 2 to 4 acute GVHD in URD HCT patients who received vorinostat and tacrolimus/methotrexate after myeloablative conditioning was 22%.• HDAC inhibition with vorinostat shows potential efficacy for GVHD prevention and should be investigated in a randomized phase 3 trial.The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in settings of heightened clinical risk that use myeloablative conditioning, unrelated donor (URD), and methotrexate are not known. We conducted a prospective, phase 2 study in this higher-risk setting. We enrolled 37 patients to provide 80% power to detect a significant difference in grade 2 to 4 acute GVHD of 50% compared with a reduction in target to 28%. Eligibility included adults with a hematological malignancy to receive myeloablative HCT from an available 8/8-HLA matched URD. Patients received GVHD prophylaxis with tacrolimus and methotrexate. Vorinostat (100 mg twice daily) was started on day 210 and continued through day 1100 post-HCT. Median age was 56 years (range, 18-69 years), and 95% had acute myelogenous leukemia or high-risk myelodysplastic syndrome. Vorinostat was safe and tolerable. The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 22%, and for grade 3 to 4 it was 8%. The cumulative incidence of chronic GVHD was 29%; relapse, nonrelapse mortality, GVHD-free relapse-free survival, and overall survival at 1 year were 19%, 16%, 47%, and 76%, respectively. Correlative analyses showed enhanced histone (H3) acetylation in peripheral blood mononuclear cells and reduced interleukin 6 (P 5 .028) and GVHD biomarkers (Reg3, P 5 .041; ST2, P 5 .002) at day 30 post-HCT in vorinostat-treated subjects compared with similarly treated patients who did not receive vorinostat. Vorinostat for GVHD prevention is an effective strategy that should be confirmed in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT01790568. (Blood. 2017;130(15):1760-1767

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Section: Introductionmentioning

confidence: 99%

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

Choi

Braun

Henig

et al. 2017

Blood

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“…Allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment option for patients with relapsed or refractory Hodgkin lymphoma (HL), [1][2][3] particularly in those for whom a previous autologous transplantation failed. Although long-term disease control can be achieved after allo-HCT, relapse remains frequent with the probability of progression-free survival (PFS) ranging from 20% to 60% at 3 years.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma

Herbaux

Gauthier

Brice³

et al. 2017

Blood

204

163

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Key Points• PD-1 blockade with nivolumab provides durable disease control after allo-HCT.• PD-1 blockade with nivolumab after allo-HCT is associated with 30% acute GVHD.Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is still frequent. The programmed cell death protein 1 (PD-1) pathwayblocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients died as a result of GVHD, 1 of progressive disease and 1 of complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, the 1-year progression-free survival rate was 58.2% (95% CI, 33.1%-76.7%) and the overall survival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile. (Blood. 2017;129(18):2471-2478

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“…3 , Beatriz stela Gomes de souza PitomBeira arauJo 3 , clara maria Bastos eloy da costa 4 , acy teles quixadá-medica 5 , Jacqueline de souza holanda 5 , samuel Vasconcelos landim 6 , maria helena PitomBeira Hematology Service, where they are seen in the PreTransplantation Outpatient Clinic for reassessment of BMT indication. Patients are referred with their respective medical records from the original service, containing the biopsy diagnosis report, immunohistochemistry, chemotherapy and radiotherapy protocols performed, date of recurrence or whether the patient is refractory to treatment.…”

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confidence: 99%

Hodgkin’s Lymphoma - evaluation of patients submitted to Autologous transplantation of hematopoietic cells in the Hematology Service of the Hospital Walter Cantídio – Fortaleza, Brazil.

Duarte¹,

Fernandes

Kaufmann³

et al. 2016

Rev. Assoc. Med. Bras.

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SUMMARY The Autologous HSCT is an important alternative for refractory or recurrent HL patients in terms of survival and improved quality of life. This study analyzes the results of autologous BMT performed in HL patients in the Transplant Unit of the HUWC/ HEMOCE (Fortaleza - CE, Brazil). Fifty-two transplanted patients were studied from January 2009 to October 2015, among them, 30 men and 22 women, mean age of 28.2 years. All of them received GCS-F during the mobilization, in some cases associated with Vinorelbine or Plerixafor, with CD34 collection averaging 4.8 CD34/kg. The conditioning was performed with BEAC, NEAM or BEAM and the grafting with an average of 10 days. The evaluation on D + 100 showed: CR - 42 (82.7%), PR - 08 (13.5%) and 02 (3.8%) deaths, three and six days after cell infusion. After the D+100, 08 patients in CR showed HL recurrence from 06 to 36 months; 03 died and 05 are being treated with brentuximab; among the 08 patients in PR, 01 died due to HL activity, 04 months after BMT and 07 patients are undergoing treatment. The final evaluation of HL transplant patients showed an OS of 88.5% and a DFS of 61.5% in 6 years, with OS of the chemosensitive patients of 81% and of the chemoresistant ones, of 72.6%. It is possible to conclude that the Autologous HSCT has shown to be an excellent rescue therapy regarding tolerance, as well as the overall survival.

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Allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma: a systematic review and meta-analysis

Cited by 71 publications

References 48 publications

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma

Hodgkin’s Lymphoma - evaluation of patients submitted to Autologous transplantation of hematopoietic cells in the Hematology Service of the Hospital Walter Cantídio – Fortaleza, Brazil.

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