scholarly journals Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant?

2020 ◽  
Vol 9 (8) ◽  
pp. 2354
Author(s):  
Hyunkyung Park ◽  
Ja Min Byun ◽  
Sung-Soo Yoon ◽  
Youngil Koh ◽  
Dong-Yeop Shin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Optimal Timing ◽  
Term Survival ◽  
One Year

Background: Despite offering an attractive option, the role of allogeneic stem cell transplantation (alloSCT) for treatment of multiple myeloma (MM) remains unclear. Methods: Recognizing the paucity of data in the Asian population, we retrospectively evaluated the outcomes of 24 patients (median age 52) undergoing alloSCT between April 2003 and November 2017. Results: The median time from diagnosis to alloSCT was 39.4 months. The majority of the patients (70.8%) underwent alloSCT followed by reduced intensity conditioning regimens after a median of five lines of therapy. Among 24 patients, 15 patients (62.5%) had a high-risk MM feature. The two-year relapse-free survival (RFS) and overall survival (OS) of the total patients were 29.2 ± 9.3% and 44.3 ± 10.3%, respectively. Patients who were treated with less chemotherapy lines (<5) before alloSCT had a prolonged RFS and OS. All patients (seven patients) who received a myeloablative conditioning regimen had high-risk features, but two out of seven patients showed long-term survival without lasting sequelae. Nine patients (37.5%) experienced non-relapse mortality (NRM) within one year after alloSCT (the one-year cumulative incidence of NRM was 38.3 ± 10.1%). Conclusion: AlloSCT can still be implemented as effective salvage option in the treatment of relapsed/refractory high-risk MM. The optimal timing of alloSCT remains to be determined.

Durable Remission after Prophylactic Donor Lymphocyte Transfusion Following Allogeneic Stem Cell Transplantation with Reduced Conditioning for High-Risk AML and MDS.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 299-299
Author(s):  
Michael Schleuning ◽  
Christoph Schmid ◽  
Georg Ledderose ◽  
Johanna Tischer ◽  
Meike Humann ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Chronic Infections ◽  
Term Survival

Abstract Prophylactic transfusion of donor lymphocytes (pDLT) is an attractive form of maintenance therapy after allogeneic stem cell transplantation in patients with high risk of relapse. However, clinical experience is limited, and disease response is often achieved at the expense of severe graft-versus-host disease (GvHD). We here report our data on pDLT in high-risk AML and MDS. Cells were given within a prospective protocol that contained a sequence of chemotherapy, reduced intensity conditioning for allogeneic transplantation, and pDLT (FLAMSA-regimen). For pDLT, patients had to be in CR at least 120 days from transplantation, off immunosuppression for 30 days, and free of GvHD. 22/86 patients alive at day +120 fulfilled the criteria for pDLT. They had been transplanted for refractory or relapsed leukemia (n=9 each) or in CR1 because of unfavorable cytogenetics (n=4). 14 patients had an unfavorable karyotype, 8 with complex aberrations. Reasons for withholding pDLT in 64 patients included cGvHD or prolonged immunosuppression (n=38), refractory or relapsed leukemia (n=15), refusal of patient or donor (n=4 each), a history of grade IV acute GvHD (n=2), and chronic infections (n=3). The median time from transplant to first pDLT was 167 days (range 120–297). Median follow up of transfused patients is 696 days (range 209–1341). Ten patients received 1, 6 patients received 2, and 6 patients received 3 transfusions in escalating doses, containing a median of 1x106, 5x106 and 1x107 CD3+ cells/kg at pDLT 1, 2 and 3, respectively. Reasons for giving less than 3 transfusions were GvHD, relapse or refusal of the patient. Induction of GvHD was the main complication; grade III acute GvHD developed in 1, and chronic GvHD in 7 patients. So far, 5 patients have relapsed despite pDLT. One died of refractory leukemia, whereas 2 achieved secondary CR following adoptive immunotherapy. Two patients are currently under treatment. At present, 18/22 patients are alive and in CR at a median of 423 days post DLT. The current leukemia free survival at two years from first pDLT is 79%. Nineteen patients were complete chimeras at time of pDLT. pDLT converted mixed into complete bone marrow chimerism in 1, but failed in 2 cases. In our experience, pDLT is safe after allogeneic transplantation for high risk AML, when given at low doses and to a selected group of patients. Results are encouraging, and long term survival can be achieved. However, further studies need to define more precisely the contribution of pDLT to the therapeutic effect of the entire procedure.

scholarly journals Long-term survival after allogeneic stem cell transplantation for advanced stage multiple myeloma

2014 ◽  
Vol 166 (4) ◽  
pp. 616-618 ◽  
Author(s):  
Marie-Christiane Vekemans ◽  
Lucienne Michaux ◽  
Eric Van Den Neste ◽  
Augustin Ferrant
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Stage ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Allogeneic Stem Cell Transplantation in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Christine Greil ◽  
Monika Engelhardt ◽  
Jürgen Finke ◽  
Ralph Wäsch
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Groups ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

Lenalidomide Followed with Donor Lymphocytes Infusion (DLI) After Allogeneic Stem-Cell Transplantation (Allo-SCT) with Reduced-Intensity Conditioning in Patients with High Risk Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4310-4310
Author(s):  
Jean El-Cheikh ◽  
Roberto Crocchiolo ◽  
Patrick Ladaique ◽  
Sabine Furst ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Donor Lymphocyte Infusion ◽  
Peripheral Blood Stem Cells

Abstract Abstract 4310 Purpose: Relapse remains the main issue after allogeneic stem cell transplantation (Allo-SCT) in high risk Multiple Myeloma (MM) patients. The aim of this study is to assess the anti-myeloma effect of lenalidomide followed by donor lymphocyte infusion (DLI) as adoptive immunotherapy after transplantation. Patients and methods: Twelve patients with refractory and high risk myeloma were analyzed. Median age at transplantation was 56 years (46–64); 6 patients (50%) received lenalidomide before Allo-SCT. All patients received a RIC including Fludarabine 30 mg/m2 5 days, ATG 2,5 mg/kg for 2 days and Busilvex 3.2 mg/kg/day (3 days in 6 patients and 2 days in 6 patients). All but one received peripheral blood stem cells (PBSC). Donor was HLA id in 6 patients and matched unrelated in 6 patients. It is our standard long term practice to consider post-transplant DLI in patients with progressive or persistent disease after day 100 if no GVHD signs were evident. In 2010, we introduced the use of lenalidomide after day 100 in patients with MM presenting the same characteristics. Doses ranged from 10 to 25 mg/day. Lenalodomide treatment could be completed with DLI, administered afterward, at least after 2 cycles. Results: The median time between Allo-SCT and lenalidomide was 10 months (3–38). The median initial dose of lenalidomide was 15 mg (10–25). Patients received a median of 6 cycles (1–10). Nine patients (60%) received an escalating dose of DLI; 1 × 107/Kg of CD3+cells for the first DLI and 1 × 108/Kg of CD3+cells for the second DLI. One patient with GVHD (after tapering of the cyclosporine A and only after 10 days of lenalidomide) and two patients with progressive disease after lenalidomide did not receive DLI. The toxicity related to lenalidomide was mainly haematological (grade II in 4 patients (33%) and grade I in 3 patients (25%); 7 patients (58%) had moderate asthenia. One patient developed a reversible renal insufficiency after 10 cycles of lenalidomide, none of our patients developed thrombo-embolism under treatment. At the last follow up, 9 patients are alive and all of them are under ongoing treatment. Four patients achieved complete remission (CR) and five patients partial remission at last evaluation. The 1 and 2 years probability of the progression-free survival (PFS) was 75% and 50% and overall survival (OS) was 83 % and 69% respectively. The median OS was not reached and the median PFS was 23 months. Conclusions: These data show that lenalidomide has an acceptable toxicity. Combination with DLI should be further evaluated in a larger cohort of patients. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation after Conditioning with Treosulfan, Etoposide and Cyclophosphamide for Patients with Acute Lymphoblastic Leukemia (ALL) Not Eligible for TBI-Containing Regimens: A Phase II-Study on Behalf of the German ALL Study Group (GMALL) and the German Cooperative Transplant Study Group

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2461-2461
Author(s):  
Nicolaus Kröger ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
Uwe Pichlmeier ◽  
Christoph Schmid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
One Year ◽  
First Complete Remission

Abstract Total-body-irradiation (TBI) based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with acute lymphoblastic leukemia (ALL). Within a multi-center prospective phase II study we have investigated the toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide, and cyclophosphamide in patients with ALL. Inclusion criteria were complete remission, non-eligibility for TBI or patient’s wish to avoid TBI. Between July 2007 and August 2010, 50 patients with a median age of 46.5 years were enrolled at ten German centers. 74% of the patients were in 1. CR and 26% 2. or higher CR.The conditioning regimen consisted of treosulfan (12 g/m²) given intravenously on three consecutive days (-7, -6, and -5) plus etoposide (30 mg/kg BW) infused on day -4, and cyclophosphamide (60 mg/kg BW) intra­venously on day -3 and -2. GvHD prophylaxis consisted of ATG-Fresenius (Fresenius Biotech, Gräfelfing, Germany), 20 mg/kg on day -3, -2, and -1 for unrelated donors, and optional for matched related donors. All patients received cyclosporine A and short course methotrexate (days 1, 3 and 6). Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. Primary graft-failure was observed in three patients. The toxicity was moderate including VOD in four patients. Acute graft-versus-host disease (GvHD) grade II - IV and grade III/IV was noted in 53 % and 14 %, respectively. Chronic GvHD at one year was seen in 41 %, which was extensive in 14 %. After a median follow-up of 24 months, the cumulative incidence of non-relapse mortality (NRM) at one year was 8 %, and of relapse 36 % and 51 % at one and two years, respectively. Patients in first complete remission showed a 12-months relapse-rate of 23 % compared to 69 % in patients beyond first complete remission. After 24 months, the respective rates were 34 % compared to 92 %. The estimated 2-year disease-free and overall survival was 36 % and 48 %, respectively. Patients in first complete remission experienced a median DFS of 25.7 months versus 8.9 months in patients beyond first complete remission. The 12- and 24-months DFS-rates were 69 % and 50 %, respectively, compared to 23 % and 0 %, respectively. Overall, we conclude that a conditioning regimen containing treosulfan, etoposide, and cyclophosphamide resulted in a low NRM , but a high risk of relapse in 2. or higher complete remission. This regimen might represents an alternative therapy for patients with ALL in 1.complete remission who need allogeneic stem cell transplantation but are not eligible for total-body irradiation. (registered under NCT00682305) Disclosures Kröger: Medac: Research Funding; Fresenius: Research Funding; Pierre Fabre: Research Funding. Off Label Use: Treosulfan is not approved for stem cell transplantation. Kobbe:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other.

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