scholarly journals Unrelated donors are associated with improved relapse-free survival compared to related donors in patients with myelodysplastic syndrome undergoing reduced intensity allogeneic stem cell transplantation

2016 ◽  
Vol 91 (9) ◽  
pp. 883-887 ◽  
Author(s):  
Clinton Yam ◽  
Lisa Crisalli ◽  
Selina M. Luger ◽  
Alison W. Loren ◽  
Elizabeth O. Hexner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Unrelated Donors ◽  
Reduced Intensity

Reduced Intensity Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma Is Associated with Substantial Late Transplant Related Mortality and a Poor Outcome in Patients with Chemoresistant Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2260-2260 ◽  
Author(s):  
Stephen P. Robinson ◽  
Norbert Schmitz ◽  
Goli Taghipour ◽  
Anna Sureda
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell ◽  
Reduced Intensity ◽  
Related Mortality

Abstract The prognosis for patients with mantle cell lymphoma (MCL) treated with conventional chemotherapy remains poor. Dose escalation and stem cell transplantation has been increasingly employed in an attempt to improve the outcome in these patients. However, due to the advanced age of many patients with MCL, high dose therapy and allogeneic stem cell transplantation is particularly hazardous. Reduced intensity allogeneic transplantation (RIT) may reduce the toxicity of allogeneic stem cell transplantation, facilitate allogeneic engraftment and graft versus lymphoma reactions. However, the results reported to date with this treatment modality have been based on small numbers of patients and provide conflicting results. We have therefore analysed the outcome of a large cohort of patients with MCL reported to the EBMT registry who have undergone RIT. A total of 144 patients (123 male) with a histological diagnosis of MCL were reported by 81 centres. The median age at transplant was 49 years (range 28–68 years) and the median time from diagnosis to transplant was 25 months (range 0.25–13.2 years). The patients had received a median of 2 (range 1–5) lines of prior chemotherapy and 60 (42%) had undergone a prior high dose procedure. At the time of RIT 100 patients had chemosensitive disease, 22 chemoresistant disease and 22 had untested relapse. Patients underwent conditioning with reduced intensity regimens prior to transplantation with allogeneic peripheral blood stem cells (122), bone marrow (20) or both (1). Fully matched sibling donors were used in 109 cases, matched unrelated donors in 21 and 9 patients received mismatched stem cells. 123 of 126 patients assessable for engraftment demonstrated sustained engraftment. With a median follow up of 9 months 84 patients remain alive and 60 have died (15 from progressive disease and 45 from non-relapse mortality). The transplant related mortality (TRM) was 12% at 100 days but by Kaplan-Mier analysis the TRM was 35% at 1 year and 50% at two years. In univariate analysis there was a non-significant trend to a higher TRM in patients with chemoresistant disease (p=0.067) and those with a prior transplant (p=0.062). Patient age and the number of lines of prior therapy had no impact on TRM. At two years following transplant 57% of patients had evidence of disease relapse or progression which was significantly worse in those with chemoresistant disease prior to transplant (p=0.02). The overall survival (OS) at 1 year and 2 years was 55% and 31% respectively and was worse for patients with chemoresistant disease. The progression free survival (PFS) at 1 and 2 year was 43% and 26% respectively. Only disease status at transplantation predicted for a worse PFS. Acute GVHD (grade II-IV) developed in 52 patients and chronic GVHD in 23 patients. Although the early transplant related toxicity is low there remains a significant TRM following RIT for MCL and consequently a low progression free survival. Patients with chemoresistant disease have a particularly poor outcome.

Two-Year Follow-Up Results at the M.D. Anderson Hospital with Reduced-Intensity Allogeneic Stem Cell Transplantation with Fludarabine-Melphalan as Preparative Regimen in Relapsed/Refractory Hodgkin’s Lymphoma: Comparable Outcome with Matched Related and Unrelated Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3115-3115 ◽  
Author(s):  
Paolo Anderlini ◽  
Rima M. Saliba ◽  
Sandra Acholonu ◽  
Sergio A. Giralt ◽  
Issa F. Khouri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Unrelated Donors ◽  
Reduced Intensity

Abstract BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) is gaining increasing acceptance in relapsed/refractory (R/R) Hodgkin’s lymphoma (HL), but there are little or no outcome data with matched unrelated donors (MUDs). METHODS: Fifty-eight patients with relapsed or refractory Hodgkin’s lymphoma (HL) underwent allogeneic stem cell transplantation (allo-SCT) following a reduced-intensity conditioning (RIC) regimen from a matched related donor (MRD; n=25) or a matched unrelated donor (MUD; n=33). The median age was 32 years (range 19–59). The median number of chemotherapy regimens received prior to allo-SCT was five (range 2–9). Forty-eight (83%) patients had received a prior autologous (auto) SCT. The median time to progression after auto-SCT was five months (1–34). Disease status at SCT was sensitive relapse (n=30) or refractory relapse (n=28). The conditioning regimen employed was fludarabine (125–130 mg/m sq over 4–5 days), melphalan (140 mg/m sq IV over 2 days) (FM) and antithymocyte globulin (thymoglobulin 6 mg/kg over 3 days) was added for the most recent fourteen MUD transplants. Graft-vs-host disease (GVHD) prophylaxis included tacrolimus and mini-methotrexate. RESULTS: Chimerism studies indicated 100% donor-derived engraftment in all patients (100%). Cumulative 100-day and 2-year transplant-related mortality (TRM) were 7% and 15%, respectively, (100-day TRM MRD vs. MUD 6% vs. 8%, p=ns; 2-year MRD vs. MUD 13% vs. 16%, p=ns). The cumulative incidence of acute (grade II–IV) GVHD (first 100 days) was 28% (MRD vs. MUD 12% vs. 39%, p=0.04). The cumulative incidence of chronic GVHD at any time was 74% (MRD vs. MUD 57% vs. 89%, p=0.003). Fourteen pts (24%) received a total of 25 (range 1–5) donor leukocyte infusions (DLIs) for disease progression/relapse (PD). Five of them (35%) received salvage chemotherapy as well, and nine (64%) developed acute GVHD after the DLI. Thirty-six patients (62%) are alive (23 in remission) with a median follow-up of 24 months (4–78). The f/up is 23 months (4–53) for alive pts always in remission. Twenty-two patients (38%) expired, and relapse-related mortality was 24%. Projected 2-year overall (OS) and progression-free (PFS) survival are 64% (49–76) and 32% (20–45), with projected 2-year PD at 55% (43–70). There was no statistically significant difference between MRD and MUD transplants with regard to OS (p=0.1), PFS (p=0.9) and PD (p=0.8). There was a clear trend for the response status prior to allo-SCT (complete response, complete response undefined vs. all others) to favorably impact PFS (p=0.07) and PD (p=0.049), but not OS (p=0.4). Partial responders and patients with stable or refractory disease fared similarly with regard to OS and PFS. CONCLUSIONS: Despite the expected higher incidence of acute and chronic GVHD, MUD RIC allo-SCTs had TRM, PFS, and OS comparable to MRD allo-SCTs. Day 100, 2-year TRM and OS/PFS data appear very encouraging in these very high-risk, extensively pretreated patients. Response status at transplant seems to affect outcome, and PD remains a major obstacle. The use of unrelated donors would greatly expand donor availability for these patients.

Impact of the New Anti-Myeloma Drugs on Outcome of Allogeneic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with High-Risk Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4456-4456
Author(s):  
Jean El-Cheikh ◽  
Roberto Crocchiolo ◽  
Jean Marie Boher ◽  
Sabine Furst ◽  
Anne Marie Stoppa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Graft Versus Host ◽  
Significant Difference ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 4456 The increasing use of the novel agents, lenalinomide and bortezomib, in the treatment of multiple myeloma (MM) has contributed to higher complete remission (CR) rates and longer overall (OS) and event free survival (EFS). We assessed the impact of these drugs on the outcome of high-risk MM patients treated with allogeneic stem-cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) over the last 10 years in our program. This retrospective study compared 45 patients (group1) transplanted in our centre between January 1999 and January 2006 and who had not received either novel agent prior to transplant (as induction or relapse therapy) with 34 patients (group 2) transplanted between January 2006 and June 2010 who received either one or both drugs before allo-SCT. The median time between diagnosis and Allo-SCT was 37 months (6–161) and 41 months (9–145) in the two groups respectively (p=NS). The median time between auto-SCT and allo-SCT was 9 months (2–89) and 27 months (2–49) respectively (p<0.0001). 36 patients (80%) in the first group vs. 8 patients (24%) in the second group received a tandem auto allo-SCT (p<0.0001). The disease status at transplantation was in CR in 2 patients (4%) vs. 10 patients (29%) and PR or stable disease in 35 patients (78%) vs. 21 patients (62%) in the first and the second group respectively (p<0.0033). in the table 1 we resumed some important data. Table 1Table 1:Patients Characteristic:Characteristics n=791999-2006 n=45 (57%)2006-2010 n=34 (43%)Fisher, p valueMedian age years (range)51 (27-65)55 (39-67)Number of prior therapies 1 2318 (40) 17 (38) 10 (22)8 (24) 18 (52) 8 (24)0.1509Cytogenetics at diagnosis Normal Del(13) Del (17) t (4;14) NA5 (11) 4 (9) 36 (80)3 (9) 12 (35) 19 (56)0.00504Disease status CR ou VGPR PR ou SD PD or refractory2 (4) 35 (78) 8 (18)10 (29) 21 (62) 3 (9)0.003359Donor type Matched Sibling Unrelated Donor45 (100) 021 (62) 13 (38)0.0004517Conditioning treatment With TBI With ATG19 (42) 26 (58)9 (26) 25 (74)0.1632Legend: Allo-SCT, allogeneic stem cell transplantation; Auto-SCT, autologous stem cell transplantation; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease. GVHD indicates graft-versus-host disease; CSP, cyclosporine; MMF, mycofenolate mofetyl; TBI, total-body irradiation; ATG, anti-thymoglobulin; TRM, Transplant related mortality. Groups differ in several aspects: In recent years allogeneic transplant was considered rather as salvage therapy in patients relapsing after auto-SCT than in a tandem auto-allo strategy, patients with cytogenetic aberrations (p<0.005), and stem cell source from unrelated donor (13 patients (38%) vs. none) (p<0.0004), and two days of anti-thymoglobuline (ATG 2,5mg/kg/day). (P<0.001), in the second group. Table 1 The median follow-up after transplant was 45 (2–127) and 16 (3–39) months in the first and second group respectively (p<0.001). The cumulative incidence of acute graft versus-host disease (GVHD) tended to be higher before 2006 (47% vs. 24%; p=0.0584). The cumulative incidence of chronic GVHD was statistically different (56% vs. 30%; p=0.0241). The estimated probability of TRM at day 100 was 12% in the first group vs. 0 % in the second group (p=0.077) and did not differ between groups at 2 years. (18% vs. 23% (p =0.537)). The overall survival (OS) at two years was 60% vs 70% in the first and second group respectively (p=0.1784). The progression-free survival (PFS) tended to be different at 2 years (45% vs. 65% (p=0.056)). The median of PFS is 22 months for patients transplanted prior 2006 and is not reached in the second group (p=0.1811). In our study there was no significant difference in OS or TRM between the 2 groups in multivariate analysis; only the number of previous auto-SCT with more than two high dose chemotherapies has a negative impact on the OS. There was a significant difference in the incidence of relapse between the 2 groups in the multivariate analysis. Although we cannot carry out the impact of other changes related to our practice in the same period, these data suggests an impact in transplant outcomes of novel drugs introduced in the therapy of MM (lower TRM, GVHD and higher disease control). This piece of information, if confirmed, should be taken into considerations for present and future approaches. Disclosures: No relevant conflicts of interest to declare.

Reduced intensity allogeneic stem cell transplantation in patients with myelodysplastic syndrome: Does the conditioning matter? A retrospective study of the SFGM-TC on 61 patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6547-6547
Author(s):  
L. Terriou ◽  
Z. Chir ◽  
H. Esperou ◽  
J. Boiron ◽  
N. Gratecos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
The Impact ◽  
Reduced Intensity

6547 Background: Reduced-intensity allogeneic stem cell transplantation (RIT) has emerged as an alternative to myeloablative transplantation in pts with myelodysplastic syndrome (MDS). Given the uncertainty regarding the appropriate conditioning, SFGM-TC conducted a retrospective multicenter study with the attempt to evaluate the impact of conditioning on pts’ outcome. Methods: The record of 61 pts (37 males) with MDS who received a RIT between 1998 and 2003, from 22 French transplantation centres, were reviewed. According to the FAB classification, 11 pts had RA at diagnosis, of whom one had progressed to REAB and one to AML before transplantation. Thirty-two pts had REAB, of whom 2 had progressed to REAB-T and 7 to AML. Twelve pts had REAB-T and 6 CMML, of whom 8 progressed to AML. The median time from diagnosis to RIT was 12 months (6–129). Conditioning regimen consisted of fludarabin (Flu) plus busulfan ( n=29), Flu plus 2-Gy TBI ( n=20) and idarubicin plus aracytine and Flu (n=12). Donors were HLA-identical siblings (n=52) and HLA-matched unrelated (n=9). All pts received peripheral blood stem cells. The median of CD34+ infused cell dose was 5 × 106/kg (0.5–17.3). Results: At the reference date of 1 July 2005, median follow-up was 44.7 months (21–85). Estimated 3-year overall survival (OS), progression free survival (PFS), relapse and transplant-relapse mortality (TRM) were 35%, 27%, 66% and 30%, respectively. Neither of the 3 conditioning regimens used had impact on pts’ outcome. In multivariable analyses, while acute III/IV grade GVHD development was the only factor found to adversely influencing OS (HR=3.6; 95% CI: 1.1–12.2), chronic GVHD development was the only favourably influencing PFS and relapse ratios (HR=0.3; 95% CI: 0.1–0.7 and HR=0.2; 95% CI: 0.1–0.6, respectively). TRM was adversely influenced by male sex of pt (HR=9.2; 95% CI: 1.5–66.6). Conclusions: RIT seems to be an effective treatment in MDS pts irrespective of conditioning type. While acute III/IV grade GVHD appeared to be detrimental, the benefit effect of chronic GVHD was to be bound to GVL effect. New approaches with focus on immunosuppressive treatment are needed to enhance the GVL effect with an acceptable risk of GVHD. No significant financial relationships to disclose.

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