scholarly journals Stem-Cell Transplantation in Adult Patients with Relapsed/Refractory Hodgkin Lymphoma

2021 ◽  
Vol 2 (4) ◽  
pp. 396-411
Author(s):  
Sonja Genadieva Stavrik ◽  
Anna Sureda
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Unmet Need ◽  
Young Patients ◽  
New Drugs ◽  
First Line

Although the majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy, in 85–90% of early stage and 70–80% of advanced-stage disease cases, relapse remains a major problem. Autologous stem-cell transplantation (auto-HCT) after salvage chemotherapy is currently considered to be the standard of care for patients who relapse after first-line chemotherapy or for whom first-line treatment fails. The curative capacity of auto-HCT has been improving with the introduction of new drug-based salvage strategies and consolidation strategies after auto-HCT. Allogeneic stem-cell transplantation (allo-HCT) represents a reasonable treatment option for young patients who relapse or progress after auto-HCT and have chemosensitive disease at the time of transplantation. Allo-HCT is a valid treatment strategy for patients with relapse/refractory HL (r/r HL) because the results have improved over time, mainly with the safe combination of allo-HCT and new drugs. Bearing in mind that outcomes after haploidentical stem-cell transplantation (haplo-HCT) are comparable with those for matched sibling donors and matched unrelated donors, haplo-HCT is now the preferred alternative donor source for patients with r/r HL without a donor or when there is urgency to find a donor if a matched related donor is not present. The development of new drugs such as anti-CD 30 monoclonal antibodies and checkpoint inhibitors (CPI) for relapsed or refractory HL has demonstrated high response rates and durable remissions, and challenged the role and timing of HCT. The treatment of patients with HL who develop disease recurrence or progression after allo-HCT remains a real challenge and an unmet need.

scholarly journals Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center

2021 ◽  
Vol 27 ◽  
Author(s):  
A. Kopińska ◽  
A. Koclęga ◽  
A. Wieczorkiewicz-Kabut ◽  
K. Woźniczka ◽  
D. Kata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Disease Status ◽  
Term Survival ◽  
Entire Cohort

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach.Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting.Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020.Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%.Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

scholarly journals Immunotherapy in myeloma: how far have we come?

2019 ◽  
Vol 10 ◽  
pp. 204062071882266 ◽  
Author(s):  
Laurens E. Franssen ◽  
Tuna Mutis ◽  
Henk M. Lokhorst ◽  
Niels W. C. J. van de Donk
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
New Drugs ◽  
High Rate ◽  
High Dose ◽  
Cell Surface Antigens ◽  
Term Survival

The treatment of multiple myeloma (MM) has evolved substantially over the past decades, leading to a significantly improved outcome of MM patients. The introduction of high-dose therapy, especially, and autologous stem cell transplantation, as well as the development of new drugs, such as immunomodulatory drugs (IMiDs) and proteasome inhibitors have contributed to the improvement in survival. However, eventually most MM patients relapse, which indicates that there is a need for new agents and novel treatment strategies. Importantly, the long-term survival in a subset of MM patients after allogeneic stem cell transplantation illustrates the potential of immunotherapy in MM, but allogeneic stem cell transplantation is also associated with a high rate of treatment-related mortality. Recently, a better insight into several immune-evasion mechanisms, which contribute to tumor progression, has resulted in the development of active and well-tolerated novel forms of immunotherapy. These immunotherapeutic agents can be used as monotherapy, or, even more successfully, in combination with other established anti-MM agents to further improve depth and duration of response by preventing the outgrowth of resistant clones. This review will discuss the mechanisms used by MM cells to evade the immune system, and also provide an overview of currently approved immunotherapeutic drugs, such as IMiDs (e.g. lenalidomide and pomalidomide) and monoclonal antibodies that target cell surface antigens present on the MM cell (e.g. elotuzumab and daratumumab), as well as novel immunotherapies (e.g. chimeric antigen receptor T-cells, bispecific antibodies and checkpoint inhibitors) currently in clinical development in MM.

Impact of CRi on the Outcome of Elderly Patients with Untreated Acute Myeloid Leukemia (AML)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2988-2988 ◽  
Author(s):  
Anne Etienne ◽  
Aude Charbonnier ◽  
Thomas Prebet ◽  
Diane Coso ◽  
Evelyne D’Incan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Disease Free Survival ◽  
Complete Response ◽  
New Drugs ◽  
Remission Induction ◽  
First Line ◽  
Allogenic Stem Cell Transplantation

Abstract New international recommendations of response for treatment of AML include morphologic complete remission with incomplete blood count recovery (CRi). This response criteria was defined following evaluation of new drugs used for the treatment of AML in first relapse (Sievers et al., JCO2001;19:3244–3254). The objective of our study was to evaluate this criterion in elderly patients with AML who are in first line of treatment. Between 1995 and 2006, 454 patients aged 55 years or older with previously untreated acute non promyelocytic leukemia received a conventional anthracycline and cytarabine induction chemotherapy in our institution. Ages were between 55 and 85 years (median 65 years). Two hundred and fourty-eight patients achieved a complete response (CR) (55%), 37 patients achieved CRi (8%), 104 patients had persisting leukemia (23%), and 49 died during remission induction therapy (13%). Multilineage dysplasia, secondary AML and blasts expressing CD34 were significantly more frequent in patients achieving CRi than CR (58% versus 29%, p=0.001, 33% versus 15%, p=0.007, and 79% versus 54%, p=0.01, respectively). No favorable prognostic karyotype was found in the CRi group but cytogenetic distribution did not differ statistically between the two groups. All patients who reached CR or CRi were scheduled to receive consolidation. Only 24 patients (65%) in CRi actually received this consolidation chemotherapy course and 11 patients (30%) had intensification (intermediate-dose cytarabine and/or autologous stem cell transplantation) whereas for patients achieving CR, 233 (94%) and 214 patients (86%) received consolidation and intensification, respectively (p<0,001 for both). None of the patients in CRi received an allogenic stem cell transplantation whereas 18 (7%) of CR patients had one (p=0,2). Disease-free survival (DFS) and remission duration were significantly different between patients in CRi and CR, with a median of 4 and 12 months, and 5 and 9 months respectively (p<0,001 and 0,03). The median overall survival (OS) was also significantly lower for patients in CRi versus CR, respectively 8 and 23 months (p<0,001). By landmark analysis, there was no difference in OS between patients in CRi and a group of 98 patients with induction failure surviving at least 60 days (p=0,4). We also noted that OS was better, in the group of patients in CRi, for those who finally achieved CR criteria after 1 or more course of post-remission chemotherapy (median 16 months, against 7 months for patients still in CRi, p=0,03). Our results show that the CRi criterion is not equivalent to CR in elderly patients who received intensive chemotherapy as the first line treatment of AML. This should be kept in mind when the results of new agents used in this setting are compared to historical data.

scholarly journals Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma

2021 ◽  
Vol 17 (2) ◽  
pp. 64-71
Author(s):  
Samer A. Al-Hadidi ◽  
Hun Ju Lee
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
High Dose ◽  
Cell Transplant ◽  
Classic Hodgkin Lymphoma

The checkpoint inhibitors nivolumab and pembrolizumab are principal treatment options for relapsed or refractory classic Hodgkin lymphoma. In patients who decline autologous stem-cell transplantation or who are unsuited for high-dose chemotherapy and subsequent autologous stem-cell transplantation because of comorbidities, the use of checkpoint inhibitors may improve overall survival and have a manageable side effect profile. This clinical review provides an evidence-based summary to guide practicing oncologists in the use of checkpoint inhibitors in relapsed or refractory classic Hodgkin lymphoma and includes checkpoint inhibitor efficacy and adverse effect profiles. We highlight the use of checkpoint inhibitors in the management of relapsed or refractory classic Hodgkin lymphoma in patients who are ineligible for an autologous stem-cell transplant with the goal of improving disease control while limiting adverse events.

Single institution experience of allogeneic stem cell transplantation for Hodgkin lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7529-7529
Author(s):  
Mauricio Pineda-Roman ◽  
Solmaz F. Afshar ◽  
Zachary Galitzeck ◽  
Amir Steinberg
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Causes Of Death ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Significant Proportion

7529 Background: Hodgkin lymphoma (HL) is curable in the majority of cases without stem cell transplantation (SCT). However, patients(pts) who relapse after chemotherapy require autologousSCT, and about half of those pts relapse. For over 3 decades, allogeneic SCT has been implemented in more refractory HL pts. We present the long term follow up of a group of pts from a our institution who underwent alloSCT for HL. Methods: 21 pts with HL transplanted from 2008 to 2015 and disease characteristics (HL type, status at SCT, chemosensitivity), treatment( graft source, donor type, auto and allo SCTdates, GVHD prophylaxis ) and outcomes (maximum grade of acute and chronic GVHD, survival (OS) and causes of death) were analyzed. Results: 13 males and 8 females received an alloSCT from 2008 to 2015, 11 pts had Nodular sclerosis HL, 6 NOS, 2 mixed cellularity, 1 lymphocyte predominant and 1 lymphocyte depleted. Performance status was 60 to 100, median of 90. 16 grafts were unrelated and 5 HLA identical. 18 pts received PBSC, 2 bone marrow and one double cord transplant. Most pts, 19, had a prior autoSCT, one had 2 prior autoSCT and for one , the allo was the first SCT. One patient was transplanted in unconfirmed first CR, 2 in confirmed CR, 4 in PR without prior CR, 3 in 1strelapse, 5 in 2nd relapse, 5 in 3rd relapse, and one in primary induction failure. All patients had a reduce intensity conditioning: 14 Flu/Mel, 4 Flu/Mel ATG, and one each Flu/TBI/ATG, Flu/TBI, Flu/Cy. Acute GVHD happened in 11 pts: max grade I in 1 , II in 7, III in 1 and IV in 2. 6 pts had extensive chronic GVHD. 12 pts (57.1%) have died (survival range 0.65-43.45 months, mean 13.1, median 6.12). Causes of death were primary disease in 4, infection in 3 pts, GVHD and infection in 2, ARDS, organ failure, pulmonary toxicity in 1 each. 9 pts (42.8%) are alive (survival range 1.63-8.44 years, mean 4.97, median 4.47) Conclusions: AlloSCT for pts with relapsed HL is a feasible treatment modality that can lead to long term OS in a significant proportion of pts. Our data is comparable with other published studies for HL alloSCT. The utility of alloSCT should not be dismissed even in the age of Brentuximab and checkpoint inhibitors.

scholarly journals Second Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma after a Previous Autograft: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3429-3429
Author(s):  
Carmen Martinez ◽  
Ariane Boumendil ◽  
Joanna Romejko-Jarosinska ◽  
Achilles Anagnostopoulos ◽  
Edgar Faber ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Allogeneic Transplantation ◽  
Brentuximab Vedotin ◽  
Karnofsky Performance Score ◽  
Hematopoietic Stem

Abstract Patients with relapsed or refractory (R/R) Hodgkin Lymphoma (HL) after first autologous stem cell transplantation (ASCT1) may be offered several therapeutic options. New agents such as brentuximab vedotin or checkpoint inhibitors have recently been approved for the treatment of these patients, however, their efficacy to provide long-term control or cure is still unknown. Thus, a significant proportion of patients are still considered candidates for a second hematopoietic stem cell transplantation, usually an allogeneic transplantation. A second ASCT (ASCT2) has historically been considered as an option only in a small group of patients so the published experience is scarce. We retrospectively evaluated the outcome of 56 adult patients (25% female/75% male) with R/R HL registered in the EBMT database who received an ASCT2 between 2005 and 2014. Planned tandem ASCT were excluded. The median age at ASCT2 was 33 years (range, 19-71) and most patients (n=46, 87%) had a Karnofsky performance score ≥80%. Forty (73%) and 9 (16%) patients were in complete remission (CR) and partial remission (PR), respectively, at day 100 after ASCT1. Twenty-six (46%) relapsed within 12 months after ASCT1. Patients received a median of 1 (0-5) treatment lines between ASCT1 and ASCT2. Of note, only 2 patients received brentuximab vedotin after ASCT1 and none of the patients in our series received checkpoint inhibitors as salvage after ASCT1. The median interval from relapse/progression to ASCT2 was 9.7 months (1.7-89.3). At the time of ASCT2, 38 (69%) patients had chemosensitive disease (20 of them CR; and 18 PR). Most patients (n=43, 77%) received BEAM as the conditioning regimen for ASCT1, whereas preparative regimens for ASCT2 were more heterogeneous (BEAM or similar in 27, 48%; CBV or similar in 8, 14%; and others in 21, 37%). The median time to neutrophil (>0.5x109/L) and platelet (>20x109/L) recovery after ASCT2 were 11 (IQR 9-12) and 12 (IQR 10-15) days, respectively. Best response at day 100 following ASCT2 included CR in 29 (52%) patients and PR in 7 (12%); 3 (5%) had stable disease, and 3 (5%) progressed. Twenty-nine (52%) patients are currently alive, with a median follow-up for surviving patients of 73 months (2-153). Causes of death were HL progression (n=21, 79%), ASCT2 toxicity (n=3, 11%), secondary neoplasia (n=1, 3.7%), and unknown (n=2, 7%). The 4-year non-relapse mortality (NRM) was 5% (95% CI 1-14%). The 4-year cumulative incidence of disease progression/relapse was 69% (95% CI 54-80%). The 4-year overall survival (OS) and progression free survival (PFS) were 63% (95% CI 51-77%) and 25% (95% CI 16-41%). In univariate analysis, HL relapse within 12 months of ASCT1 was associated with a worse 4-year OS (44% vs. 79%, p=0.016) and PFS (16% vs. 33%, p=0.033). Chemosensitivity at ASCT2 predicted for better outcomes (4-year OS 78% vs. 30%, p=0.002; PFS 34% vs. 6%, p=0.004). Our series is the largest thus far reported of ASCT2 for patients with R/R HL after ASCT1. NRM is lower than that observed after allogeneic transplantation in this setting; however, relapse remains a major issue, especially for patients who relapse in less than one year after ASCT. For this population, a second ASCT should not be considered, whereas ASCT2 in patients with long response duration after ASCT1 might be appropriate in selected cases. The role of ASCT2 for those patients treated with new drugs such as brentuximab vedotin and checkpoint inhibitors deserves further investigation. Disclosures Martinez: BMS: Research Funding; Takeda: Consultancy. Sureda:BMS: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Merck: Consultancy, Honoraria.

MODERN THERAPY FOR RELAPSES AND RESISTANT FORMS OF HODGKIN''S LYMPHOMA

2018 ◽  
Vol 64 (3) ◽  
pp. 419-428 ◽  
Author(s):  
Sergey Alekseev ◽  
Yevgeniya Kharchenko ◽  
Svetlana Kuleva ◽  
Tatyana Semiglazova
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Young Patients ◽  
High Risk Group ◽  
High Dose ◽  
Cell Transplant

Despite the success of standard front-line chemotherapy for classical Hodgkin lymphoma in part of these patients relapse or resistance are developed. During last years standard therapeutic approach for relapse or refractory disease is still «salvage» following high-dose chemotherapy with autologous stem cell transplantation. Brentuximab vedotin made great revolution in Hodgkin’s lymphoma treatment demonstrated high efficacy not only in relapse treatment but also as consolidation after autologous stem cell transplantation in high-risk group of patients. In the era of new agents for patents with relapses following autologous stem cell transplant there are multiple treatment options including single-agent and polychemotherapy, combination chemotherapy strategies, the immunoconjugate brentuximab, checkpoint inhibitors nivolumab and pembrolizumab. Allogeneic stem cell transplantation could be considered in young patients with chemosensitive tumor in the presence of a bone marrow donor. Therapeutic choice should be always based on age, comorbidities, previous treatment, patient’s preferences and drug availability.

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