Salvage Autologous or Allogeneic Stem Cell Transplantation After the Failure of First Autograft in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1186-1186
Author(s):  
Qaiser Bashir ◽  
Peter Thall ◽  
Chitra Hosing ◽  
Floralyn L Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Related Donor

Abstract Abstract 1186 Poster Board I-208 Background: Almost all patients with multiple myeloma (MM) who receive autologous hematopoietic stem cell transplantation (auto HCT) eventually relapse. The treatment options for these patients include novel agents or second (salvage) auto or allogeneic (allo) HCT. Use of reduced intensity conditioning (RIC) has significantly reduced the transplant-related mortality (TRM) with allo HCT. We evaluated the outcomes of patients who received salvage auto or allo HCT for relapsed MM. Methods: Sixty-two patients (24 females and 38 males), with a median age of 55 years (range: 37-73) received a salvage auto HCT between January 1992 and December 2008, whereas 44 patients (19 females and 25 males), with a median age of 51 years (range 32-65) received salvage allo HCT (12 unrelated and 32 related donor) between October 1988 and December 2006. Among 12 patients with unrelated allo HCT, ten were matched at 10/10 HLA loci, while two patients were mismatched at 1 or 2 loci, respectively. Among 32 patients with related donor allo HCT, 29 matched at 10/10 loci, while 3 patients had one or two antigen mismatches. In the allo HCT group eight patients received myeloablative regimens (MA), while thirty six patients received RIC regimens. MA regimens were fludarabine + melphalan 180 mg/m2 in 4 patients, busulfan + cyclophosphamide in 2 patients, busulfan + melphalan in one patient and TBI-based in another patient. RIC regimens were fludarabine + melphalan ≤140 mg/m2 in 34 patients and cyclophosphamide + fludarabine in 2 patients. Results: Median follow-up for both auto and allo HCT patients was 24 months. Median prior treatment regimens in auto and allo HCT patients were 4 (2-16) and 5 (2-10), respectively. Overall response rates in evaluable patients in auto HCT and allo HCT were 63% and 75%, respectively. Cumulative incidence of grade II-IV acute GVHD was 27% and limited or extensive chronic GVHD was 43% in allo HCT group. One-hundred day TRM in auto HCT and allo HCT groups was 3% and 9%, respectively. Most common causes of nonrelapse mortality were infections (12%) in auto, and acute or chronic GVHD (24%) in allo HCT group. Median progression free survival (PFS) and overall survival (OS) for auto HCT were 15.5 and 43.3 months, and for allo HCT were 6.9 and 14 months, respectively. Patients receiving MA regimens had significantly shorter PFS and OS than patients receiving RIC regimens. Conclusions: Both second auto and allo HCT are feasible for salvage therapy in patients with advanced MM, who had relapsed after an auto HCT. Disease progression remains the major cause of treatment failure. RIC regimens have improved the outcome of allo HCT. Disclosures: No relevant conflicts of interest to declare.

The Therapeutic Effect of Lenalidomide Is Enhanced After Allogeneic Stem Cell Transplantation: Results of a Case-Control Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1996-1996
Author(s):  
Vittorio Montefusco ◽  
Francesco Spina ◽  
Elena Zamagni ◽  
Giorgia Saporiti ◽  
Francesca Patriarca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Matching Criteria

Abstract Abstract 1996 Introduction. Lenalidomide (Len) is a highly effective drug against multiple myeloma (MM). It acts through several mechanisms, such as a direct cytotoxic effect, anti-angiogenesis, microenvironment modifications, and immunomodulation. The latter property is particularly interesting in the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) setting, since Len may interact favourably with the graft-versus-myeloma (GVM) effect. Preliminary results from retrospective studies on heterogeneous patient populations have suggested that Len is more effective when given after Allo-HSCT. In order to verify this observation, we have conducted a case-matched analysis comparing Len after autologous stem cell transplantation (Auto-HSCT) vs. Len after Allo-HSCT. The hypothesis is that Len may be more potent when administered after Allo-HSCT. Methods and results. In this retrospective study the matching criteria was represented by the number of treatment lines received before Len. In an attempt to uniform the treatment regimens, an intra-centre matching was recommended. To April 2011 we collected data from 39 patients in each group. Baseline characteristics between Auto and Allo patients were similar, except for age at diagnosis (53 years, range 39–70, in Auto patients; 47 years, range 29 – 61, in Allo patients). The median number of previous lines of treatment was 3 (range 1–6 ) for both groups. Twenty-one out 39 (54%) Allo patients received Allo-HSCT as second or subsequent line of therapy. Thirty-two (82%) Auto and 35 (90%) Allo patients received bortezomib in previous lines. Similarly, 34 (87%) Auto and 12 (54%) Allo patients were previously treated with thalidomide. Len was always combined with dexamethasone. Median time between Auto-HSCT and Len start was 38 months (range 7–159), and for Allo-HSCT 29 months (range 4–215). Best responses were for Auto and Allo patients as follows: 5 vs. 4 CR, 6 vs. 8 VGPR, 11 vs. 12 PR, 6 vs. 8 SD, 11 vs. 7 PD. Time from Len start to the best response was 4 months for both groups. With a median follow-up of 11.5 months (range 1–39), 1 year and 2 year progression-free survival were 41% and 6% for Auto patients, and 52% and 44% for Allo patients (p=0.03), respectively. Two years overall survival was 48% for Auto and 75% for Allo patients (p=0.03). Similar results were observed regardless of previous thalidomide treatment. No unexpected toxicities were reported. Two (10%) patients had worsening of a pre-existent extensive chronic GVHD. Discussion and Conclusion. The comparison between Auto and Allo patients has shown a benefit in terms of PFS and OS in favor of Len administered after AlloHSCT. This observation supports the hypothesis that Len is synergistic with the GVM effect. Since Len has a potent immunomodulatory effect, this can raise concerns about its use after AlloHSCT. A Dutch prospective study showed that the early administration of Len 10 mg daily after non-myeloablative Allo-HSCT induces late onset acute GVHD in a substantial proportion of patients, causing the premature discontinuation of the study. On the contrary, our retrospective study has shown that a later administration is feasible and safe, without an excess of GVHD, suggesting that a more mature immune system can better tolerate Len. Moreover, since in all cases dexamethasone was given in combination with Len, its immunosuppressive effect may have harnessed the Len-induced immune activation. In conclusion our study suggests that Len is particularly active after AlloHSCT, still retaining a favorable toxicity profile. Disclosures: No relevant conflicts of interest to declare.

Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 3919-3924 ◽  
Author(s):  
Nicolaus Kröger ◽  
Herbert Gottfried Sayer ◽  
Rainer Schwerdtfeger ◽  
Michael Kiehl ◽  
Arnon Nagler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Reduced Intensity

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m2), melphalan (100-140 mg/m2), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P = .04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.

Poor Mobilization of CD34+ Stem Cells Predicts Inferior Relapse and Survival Outcomes After Autologous Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3000-3000 ◽  
Author(s):  
Aleksandr Lazaryan ◽  
Hien Duong ◽  
Lisa Rybicki ◽  
Frederic J. Reu ◽  
Robert Dean ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Performance Status ◽  
Hematopoietic Stem

Abstract Abstract 3000 Autologous stem cell transplantation (ASCT) remains the standard upfront therapy of younger patients with multiple myeloma (MM). Identifying a prognostic threshold amount of mobilized CD34+ hematopoietic stem cells (SC) may become an important modifiable parameter in the era of novel stem cell mobilization strategies. While poor mobilization of CD34+ cells has been shown to cause delays in hematopoietic recovery, the data on long-term clinical outcomes of patients with inferior CD34+ SC collection (‘under mobilizers’) are limited. We analyzed prospectively collected data on 239 adult patients with MM who underwent ASCT at our institution from 01/1996 to 12/2009. Fifty-one patients (21.3%) who collected less than 4 × 106/kg CD34+ SC were classified as ‘under mobilizers’ and were compared to the rest of the study population (n=188) who collected ≥ 4 × 106/kg CD34+ SC. Even though under mobilizers were slightly older (median 59 vs. 54 years, p =0.01), had longer time from diagnosis to ASCT (11 vs. 8 months, p =0.05), and required more days of leukapheresis (5 vs. 3 days, p <0.001), they did not differ from the other group according to the number of prior treatment regimens, mobilization method (only 2 patients received plerixafor), performance status, or disease remission status at transplant (all p >0.2). Median time-to-recovery for both neutrophils (11 vs. 10 days, p <0.001) and platelets (13 vs. 12 days, p <0.001) was delayed among under mobilizers. Under mobilizers had worse relapse-free survival (RFS) (hazard ratio [HR]=1.49, 95% CI, 1.03–2.16, p =0.03) and non-relapse mortality (NRM) (HR=3.59, 95% CI, 1.51–8.56, p <0.01) in multivariable Cox proportional hazards analysis. Even though the association between poor CD34+ SC collection and inferior overall survival did not reach statistical significance (HR=1.42, 95% CI, 0.94–2.16, p =0.1), under mobilizers were found to have significantly higher rates of 100-day post-transplant mortality (p =0.02). We conclude that in the context of ASCT for MM, failure to collect ≥ 4 × 106/kg CD34+ SC is independently associated with worse RFS and NRM. Disclosures: No relevant conflicts of interest to declare.

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.

Effect of Melphalan 140 Mg/m2 Versus 200 Mg/m2 on Toxicities and Outcomes in Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1988-1988
Author(s):  
Lakshmikanth Katragadda ◽  
Lindsay McCullough ◽  
Yunfeng Dai ◽  
Jack W Hsu ◽  
John W Hiemenz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Cox Proportional Hazards Model ◽  
Hematopoietic Stem ◽  
Preparative Regimen

Abstract Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction < 50 (P=0.0001) or had Karnofsky score < 80 (P=0.01) or had creatinine > 2 either at diagnosis (P=0.004) or the time of ASCT (P=0.001). Rest of the patient and disease characteristics including Durie-Salmon stage, myeloma subtype and disease status at ASCT were not significantly different between the 2 arms. Patients in MEL-140 needed significantly longer time to ANC engraftment (P=0.037) and also had significantly higher frequency of neutropenic fever (P=0.003). There were no significant differences in mucositis (including grade), nausea, vomiting, diarrhea, bacteremia, or length of hospital stay and frequency of repeat hospitalizations among both groups. There was no treatment related mortality in either group. At a median follow up of 74 months (range, 52-140) from ASCT, there were no significant differences in relapse free survival (RFS) (P=0.4988) and overall survival (OS) (P=0.6936) between the two groups. Five year OS for MEL-140 and MEL-200 is 71.6% and 78.9%, while RFS is 23.9% and 34%, respectively. Proportion of patients whose myeloma status improved to ≥ VGPR at 3 months post ASCT was also not different (P=0.385). Importantly, similar proportions of patients received various post ASCT maintenance therapy (P=0.605). In multivariate cox proportional hazards model only disease status of ≥VGPR at the time of ASCT significantly affected RFS (P=0.024) but did not impact OS (P=0.104). Conclusion: MM patients who received MEL-140 had similar long term outcomes as those who received MEL-200 despite their older age, lower performance status and renal insufficiency. Disclosures No relevant conflicts of interest to declare.

scholarly journals Haploidentical Stem Cell Transplantation after Myeloabaltive Conditioning Is a Valid and Safe Option for Young Patients with Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma: A Study Compared with HLA-Matched Transplant

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5849-5849
Author(s):  
Haiwen Huang ◽  
Xiaofang Xiao ◽  
Jia Chen ◽  
Zhengming Jin ◽  
Xiaowen Tang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Young Patients ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract Purpose: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) therapy for refractory or relapsed (R/R) aggressive non-Hodgkin lymphoma (NHL) patients was still unknown. In this study, we aimed to explore the clinical outcome of R/R aggressive NHL patients received haplo-HSCT treatment. Patients and Methods: 23 R/R aggressive NHL patients who had undergone haplo-HSCT in our center between February 2006 and October 2015 were retrospectively analyzed, and 25 R/R aggressive NHL patients who received HLA-matched HSCT at the same period were also involved in this study. All patients received myeloablative conditioning (MAC) regimen, and antithymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. 12 patients had experienced autologous HSCT prior to allo-HSCT. Results: The median age of the total 48 patients was 33 (16-58) years old, and there were 33 males and 15 females in the total cohorts. The diagonosis were as following: 16 (33%) diffuse large B cell lymphoma and 22 (46%) peripheral T cell lymphoma. There were no difference in sex, age at transplantation, histologic diagnosis, aaIPI score, previous ASCT and conditioning regime between HLA-matched HSCT and Haplo-hsct groups. 44 patients had achieved engrafment, and the median times to neutrophil and platelet recovery were 12 and 15 days, respectively. Incidences of grade 3-4 acute GVHD were 18.3% in haplo-HSCT group and 16.7% in HLA-matched HSCT groups(p=0.87), while 2 years cumulative incidences of chronic GVHD in these two groups were 43.5% and 36.7% (P=0.68). For 16 patients who had chemoresistant disease at transplantation in haplo-HSCT group, four patients achieved complete remission, and ten patients achieved partial remission, while the other two patients experienced disease progression at 21 days and 37 days, respectively. With a median follow-up of 25 months, 12 patients experienced disease recurrence or progression in haplo-HSCT. And four patients died of transplantation related mortality: infection (n=2); acute GVHD (n=1) and multi-organ failure (n=1). There were no differences in overall survival (OS) rate at 2 years (52.8% vs 57.0%, P=0.85) and 2 years progress free survival (PFS) rate (52.7% vs 56.9%, p=0.73) between the haplo-SCT and HLA-matched SCT groups. Multivariate analyses suggested that old age (>45 years)(p=0.02), primarychemorefractory (p=0.04)and occurrence of grade3-4 aGVHD (p=0.01) may contribute to poor prognosis. Conclusion: Haploidentical hematopoietic stem cell transplantation withmyeloablative conditioning regimenachieved satisfactory outcome with acceptable side-effects. This approachcan be a feasible and acceptabletherapy for young patients withR/R NHLwho have no access to a HLA-matched donor. Figure Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Figure. Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Disclosures No relevant conflicts of interest to declare.

Single-Institute Comparable Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated and Related Donor in Patients with Myeloid Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4946-4946
Author(s):  
Shingo Yano ◽  
Noriko Usui ◽  
Nobuaki Dobashi ◽  
Yutaka Takei ◽  
Yuichi Yahagi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Myeloid Malignancies ◽  
Related Donor

Abstract Background: Allogeneic stem-cell transplantation (allo-SCT) from human leukocyte antigen identical related donor (RD) is taken priority over unrelated donor (URD), however, less than 30% of patients do not have a suitable RD. Transplantation from an URD should be considered for those patients. In order to investigate the role of URD, we retrospectively analyzed efficacy and safety of allo-SCT from URD and RD in patients with myeloid malignancies. Patients and methods: One hundred six patients with myeloid malignancies (acute myeloid leukemia 48, chronic myeloid leukemia 38, and myelodysplastic syndrome 20) who received myeloablative regimens were analyzed. The stem cell source were bone marrow from URD (n=43) and peripheral blood stem cells or bone marrow from RD (n=63). Graft-versus-host disease (GVHD) prophylaxis consisted of taclorimus and short-term methotrexate (sMTX) for URD, or cyclosporine and sMTX for RD. Results: Median follow-up was 6.3 (0.3–17.2) years, and median age of patients was 37 (15–55) years old. Hematological studies demonstrated donor engraftment in all patients. Incidence of grades II to IV of acute GVHD was 32% in URD and 18% in RD, and extended chronic GVHD was 31% in URD and 28% in RD. Probability of 8-year actuarial survival was 62% in URD and 54% in RD (p=0.4225), and 8-year disease-free survival was 64% in URD and 47% in RD (p=0.1412). There were no apparent differences in transplant-related mortality (TRM) (14% in URD and 24% in RD), relapse (14% in URD and 32% in RD) between both groups. Conclusion: These results suggested that allo-SCT from URD has comparable safety and effectiveness for adult patients with myeloid malignancies.

Reduced-Intensity Regimens for Allogeneic Stem Cell Transplantation Improve the Outcome in Advanced Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3298-3298
Author(s):  
Suzanne M. Cole ◽  
Rima Saliba ◽  
Matteo Pelosini ◽  
Floralyn L Mendoza ◽  
Donna Weber ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Opportunistic Infections ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo SCT) has two potential advantages over autologous SCT: a tumor-free graft and graft-versus-myeloma (GVM) effect. Allo SCT’s potential to induce long term remission has, however, been offset by high rates of transplant-related non-relapse mortality (TRM). Reduced-intensity conditioning (RIC) regimens for allo SCT are associated with lower TRM without compromising the GVM effect. Methods: We retrospectively analyzed our experience in 69 patients (30 females and 39 males) with heavily pretreated, relapsed myeloma, who received allo SCT at our institution between1985 and 2007. Eighteen patients received myeloablative regimens (MA), while 51 received RIC regimens. MA regimens were TBI-based in 5 patients, high-dose busulfan-containing in 6 patients and high-dose melphalan containing (180–200 mg/m2) in 7 patients. RIC regimens were a combination of fludarabine (90–120 mg/m2) and melphalan (100–140 mg/m2). Median age of patients at allo SCT in both groups was 51 years. Median interval from diagnosis to allo SCT was 35.4 months in MA group, and 34.2 months in RIC group. Eight (44%) patients in MA group and 36 (70%) patients in RIC group had prior autologous SCT. Six patients (33%) in the MA group and 11 (25%) in the RIC group received allo SCT from unrelated donors (p=0.3). Median number of prior treatment regimens were 5 (range 1–10) in both groups. Stem cell source was peripheral blood in 3 patients in MA group and 41 patients in the RIC group (p=0.0001). Results: Median follow-up in surviving patients was 27 months (3–98). All patients achieved engraftment. Cumulative TRM at 1 year was 56% in the MA group and 25% in the RIC group (p=0.03). Overall response rates in evaluable patients were 69% (CR=15%, PR= 54%) in MA group, and 79% (CR=23%, PR=56%) in the RIC group (p=0.47). Disease progression at 2 years was seen in 8 patients (44%) in the MA group and 25 patients (49%) in the RIC group (p=0.78). Median progression-free survival (PFS) in MA vs. RIC groups was 4.1 and 6.8 months, respectively (p=0.003) and median overall survival (OS) ) in MA vs. RIC group was 5.3 and 13.9 months, respectively (p=0.001). Cumulative Incidence of grade II–IV acute graft-vs.-host (GVHD) in MA vs. RIC groups disease was 33 vs. 27% (p=0.76); cumulative incidence of chronic GVHD in MA vs. RIC group was 54% vs. 47% (p=0.41) in evaluable patients. At the time of this analysis, 13 patients (25%) were still alive in RIC group, 7 of whom (14%) were in remission for up to 6 years post allo SCT. The most common causes of death were recurrent disease (30 patients; 43%), acute or chronic GVHD (16 patients; 23%) and opportunistic infections (5 patients: 7%). Conclusions: Allo SCT after RIC regimens is associated with longer PFS and OS and lower TRM. There was no increase in the risk of relapse, or acute or chronic GVHD. These regimens can safely replace MA regimens and may offer greater benefit if utilized earlier in the course of disease. Figure Figure

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