scholarly journals Allogeneic stem-cell transplantation with matched unrelated donors in elderly patients (55–67 years); age by itself is no longer a contraindication

2004 ◽  
Vol 10 ◽  
pp. 56 ◽  
Author(s):  
A. Shimoni ◽  
N. Kroger ◽  
A.R. Zander ◽  
M. Yeshurun ◽  
I. Hardan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donors

Donor Selection for Allogeneic Stem Cell Transplantation In Elderly Patients with Advanced MDS: Younger Matched-Unrelated Donor or HLA-Identical Sibling ?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 912-912
Author(s):  
Nicolaus Kröger ◽  
Tatjana Zabelina ◽  
Anja van Biezen ◽  
Axel R. Zander ◽  
Theo de Witte
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Status ◽  
Unrelated Donor ◽  
Donor Age ◽  
Matched Unrelated Donor ◽  
Unrelated Donors

Abstract Abstract 912 Allogeneic stem cell transplantation from related and unrelated donors is now a reasonable treatment option for elderly patients with advanced MDS. Retrospective studies have shown that donor age is an independent risk factor for outcome of allogeneic stem cell transplantation. By nature there is a strong correlation between patient's age and age of an HLA-identical sibling. Therefore we investigated whether a young matched unrelated donor should be preferred as donor to an elderly HLA-identical sibling in elderly MDS patients who underwent allogeneic stem cell transplantation. We extracted from the MDS-registry of the EBMT 871 patients who received allogeneic stem cell transplantation between 1986 and 2009 and fulfilled the following criterias: 1. patient's age > 50 years, 2. advanced MDS: RAEB, RAEB-t, CMML or sAML, 3. HLA-identical sibling or fully matched unrelated donor transplantation. From those 871 patients with a median age of 57 years (r., 50–73) 706 received stem cells from an HLA-identical sibling and 168 from a matched unrelated donor, either after standard conditioning (n = 387) or after reduced intensity conditioning (n = 481). After a median follow-up of 30 months, the estimated 3 years overall survival did not differ between patients who received stem cells from HLA-identical sibling or from matched unrelated donor (36 % vs. 34 %, p = 0.8). However, the median donor age was significantly higher for HLA-identical sibling than for MUD transplantation: 56 years (r: 35 – 81 y) vs. 34 years (r: 19 – 64) (p < 0.001). While age as continuous variable did not influence survival in HLA-identical sibling transplantation (HR: 1.002, p = 0.8), but did in MUD transplantation (HR: 1.03, p = 0.009), we performed 4 groups according to donor age: HLA-identical sibling transplantation with donor age > 50 years (n = 535) and donor age 30 – 50 years (n = 169) and matched unrelated transplantation with donor age < 30y (n = 60) and donor age > 30y (n = 107). These groups were well balanced according to disease-status, abnormal cytogenetics, and intensity of the conditioning regimen. The estimated 5 years OS for MUD (donorage < 30y) was 41 % and better than for HLA-identical (donor > 50y) with 31 % (p = 0.03) and HLA-identical (donor 30 – 50 y) with 33 % (p = 0.06), but worse than MUD (donor > 30 y) 24 % (p = 0.003). For overall survival, younger donors (< 30y) remained an independent factor for improved survival in a multivariate Cox model: HR: 0.66 (p = 0.03). Other factors influencing survival were disease status (sAML: HR: 1.31, p = 0.03), standard myeloablative conditioning (HR: 1.40, p = 0.002), and abnormal cytogenetic (HR: 1.26, p = 0.07). In comparison to HLA-identical sibling transplantation the hazard ratio for survival remained less than 1 for matched unrelated donors aged 20–35 years (HR: 0.66–0.99), but the hazard ration increased >1 if matched unrelated donor age becomes greater than 35 years. We conclude that for elderly patients (> 50 years) with advanced MDS who need allogeneic stem cell transplantation a younger unrelated donor should be preferred to an HLA-identical sibling donor. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5176-5176 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ronald Brand ◽  
Rodrigo Martino ◽  
Philippe Guardiola ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Working Party ◽  
Stem Cell Source ◽  
Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

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.

Is Splenectomy Necessary in Patients with Myelofibrosis and Extensive Splenomegaly Prior to Allogeneic Stem Cell Transplantation with Reduced Intensity Conditioning Regimens?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1091-1091
Author(s):  
Stefan O. Ciurea ◽  
Barry Sadegi ◽  
Andrew Wilbur ◽  
Victoria Alagiozian-Angelova ◽  
Sujata Gaitonde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Significant Risk ◽  
Primary Myelofibrosis ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
Marrow Fibrosis

Abstract Allogeneic stem cell transplantation has been shown to restore normal hematopoiesis in patients with intermediate or high risk primary myelofibrosis (PMF) or myelofibrosis preceeded by polycythemia vera or essential thrombocythemia. However, in patients with PMF and extensive splenomegaly it is not clear whether transplant is associated with an unacceptable risk or if splenectomy should be performed prior to transplant. In this study, ten consecutive patients with myelofibrosis who were not splenectomized received an allogeneic hematopoietic stem cell transplantation (HSCT) from related or unrelated donors and were periodically monitored by ultrasound or CT scan for 12 months after transplant to assess the kinetics of the reduction of splenomegaly. These findings were correlated with the time to resolution of marrow fibrosis, time to engraftment and clinical outcome. Over a 12 month period a progressive reduction in spleen size was observed in all the patients and paralleled the reduction in marrow fibrosis (Figure 1). Of 10 patients, 5 with a splenic longitudinal diameter >30 cm showed a more prolonged time to engraftment ANC> 0.5 × 109/L (d 19±5 vs 13±2, p=0.05) and platelet > 20 × 109/L (d 75±104 vs 11±2, p=0.06). However, of the 5 patients with more extensive splenomegaly only 2 experienced delayed engraftment of platelets (d 77 and 256, respectively). Full donor chimerism was observed in all patients within 60 days after transplantation regardless of the size of the spleen. At a median follow-up of 54 months (range: 2–80) all the patients are alive but 1 who died of a TTP like syndrome 2 months after transplant and had a small spleen at the time of transplant. A clinical CR has been documented in 7 patients and 2 have achieved clinical improvement as assessed by IWG response criteria. These findings suggest that allogeneic HSCT with RIC regimen can be safely performed in patients with extensive splenomegaly. Although in these patients the time to engraftment may be prolonged, the significant risk of morbidity and mortality associated with splenectomy may be avoided. Figure Figure

High-Dose Rituximab in the Conditioning Regimen Before Allogeneic Stem Cell Transplantation Reduces the Incidence of Acute Gvhd in B-Cell Lymphomas

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4546-4546
Author(s):  
Paolo Corradini ◽  
Barbara Sarina ◽  
Cristiana Carniti ◽  
Francesca Patriarca ◽  
Angelo Michele Carella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Reconstitution ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
High Dose ◽  
Unrelated Donors

Abstract Abstract 4546 Background: Reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (alloSCT) is an effective salvage therapy for relapsed lymphomas. The present GITMO study is a prospective multicenter phase II trial for patients affected by relapsed CD20 positive lymphomas. Compared with the previous thiotepa/fludarabine/cyclophosphamide GITMO protocol (Leukemia 2007), the thiotepa dose is increased, and high-dose Rituximab is included in the regimen to improve the outcome and possibly modulate the incidence of acute GVHD. Aims: Primary end-point was 1-year progression-free survival; secondary endpoints were non-relapse mortality and incidence of acute and chronic GVHD. Methods: Fifty-seven patients (pts) were enrolled so far in the study and 49 are evaluable for analysis. Treatment plan consisted of high-dose R (500 mg/ms on day -6) followed by thiotepa (12 mg/kg), fludarabine (60 mg/kg) and cyclophosphamide (60 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine and mini-methotrexate; ATG (7.5 mk/kg) was only added for pts allografted from one antigen mismatched sibling or unrelated donors. Histopathological subtypes included 24 aggressive (HG) (n= 17 diffuse large B-cell lymphomas, n= 7 mantle cell lymphomas) and 25 indolent lymphomas (LG) (n= 13 follicular lymphomas, n= 12 small lymphocytic/chronic lymphocytic leukemia). Patients were allografted from related siblings (SIB) (n= 32 matched, n=1 one single mismatched) or unrelated donors (UD) (n=11 matched, n=5 mismatched). All the pts had chemosensitive disease (n=20, 41% in complete remission) and 26 (53%) came from a failed autoSCT. Results: At a median follow-up of 13 months (range, 5–44 months), 36 pts are alive [n=27 (75%) in CR] and 13 died from any cause [n=6 for non-relapse mortality (NRM), n=7 for disease progression]. All the patients engrafted (94% had full donor chimerism at 3 months). The cumulative incidence (CI) of NRM was 13% at 1 year: 9% vs 19% for SIB and MUD (p=0.3), and 9% versus 16% for for LG and HG (p=0.3), respectively. In total only 11 of 49 pts had acute GVHD (n=8 grade II, n=3 grade III) with an estimated CI of 21% at 100 days. In the previous GITMO study the incidence was 35% with SIB only. Forty pts are evaluable for chronic GVHD with an estimated CI of 41% and 47% at 1 and 2 year, respectively (n=11 limited, n=3 extensive). Infections after engraftment requiring hospitalization or intravenous treatment were evaluable in 46 pts (n=3 excluded for early death). The overall incidence of infections was 58% (n=27) including 5 pts experienced sepsis and 10 pts pneumonia. Preliminary data on immune-reconstitution at 1 year showed: 1) low number of circulating B cells (median CD19+/ul: 129/ul) with an expansion of naive cells (IgD+, CD27-); 2) the median value of IgM was 89 mg/dl whereas IgG and IgA remained at low levels. The CI of relapse was 26% and 37% at 1 year and 2 years, respectively. In the indolent and aggressive groups, OS estimates at 2 years were 79% (95%CI, 52%-91%) and 61% (95 CI, 38%-77%) and PFS estimates were 53% (95%CI, 23%-76%) and 48% (95% CI, 27%-66%), respectively. Conclusions: The present data suggest that the administration of high-dose R is feasible and causes an unexpected reduction of the incidence of acute GVHD without increasing the NRM and the incidence of severe infections complications. Complete data evaluating the effects of R on immune reconstitution are ongoing. Disclosures: No relevant conflicts of interest to declare.

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