Faculty Opinions recommendation of HLA-mismatched unrelated donors as an alternative graft source for allogeneic stem cell transplantation after antithymocyte globulin-containing conditioning regimen.

2009 ◽  
Author(s):  
Didier Blaise
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Conditioning Regimen ◽  
Unrelated Donors

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.

A Fludarabine-Based Non-Myeloablative Conditioning Regimen in Allogeneic Stem Cell Transplantation from Related and Unrelated Donors in Chronic Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5372-5372
Author(s):  
Yi Luo ◽  
He Huang ◽  
Zhen Cai ◽  
Yamin Tan ◽  
Xiaoyan Han
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Myeloablative Conditioning ◽  
Unrelated Donors

Abstract Objective: To evaluate the efficacy and safety of a fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation (SCT)from related and unrelated donor for chronic myeloid leukemia in chronic phase(CML-CP). Methods: Fifteen consecutive patients with CML-CP between May, 2005 and July, 2006 were treated with a single non-myeloablative conditioning regimen in this study. They were 10 males and 5 females with a median age of 41 years (range, 18–49). Donors were HLA-A, B and high resolution DR fully matched siblings (n=8), matched unrelated donors (n=6), and 1-locus mismatched unrelated donors (n=1). The stem cells were collected from either peripheral blood (n=9) or bone marrow (n=6). The conditioning regimen included fludarabine 30 mg/m2/day (days -10 to -5), oral busulfan 4 mg/kg/day (n=4 patients), or intravenous busulfan 3.2 mg/kg/day (n=11 patients) (days -6 to -5) and anti-thymocyte globulin (Fresenius, Germany) (5mg/kg/day) (days -4 to-1). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease(GVHD) after transplantation. Lipoprostagandin E1 was used in prophylactic regimen for hepatic veno-occlusive disease(VOD). To assess engraftment, degree of chimerism, minimal residual disease and relapse, all patients were monitored by cytogenetic analysis and donor vs host-specific DNA markers using short tandem repeats (STR) assay. The average cell number of MNC transfused was 4.83 (3.14~11.5)×108/kg; CD34+ cells were 3.47(2.38~6.24)×106/kg, CFU-GM was 2.15 (1.85~3.06) ×105/kg. Results: Engraftment of neutrophils and platelets was achieved in 14 out of 15 (93.3%) patients within a median of 13 days (range, 8–21) and 18 days (range, 10–35), respectively. Fourteen patients achieved complete donor chimerism in the peripheral blood before day +35 and one developed graft failure. No patients developed acute GVHD and VOD, but one died from interstitial pneumonia while she was in continuous complete remission 2 months following transplantation. With a median follow-up of 5 months (range 1.5 to 15), 13 of them were still in CCR. The overall non-relapse mortality in this group was 6.67% (1/15 patients). Overall survival, and disease-free survival rates were 93.3% and 86.7%, respectively. Conclusion: A fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation from related and unrelated donors is an effective and safe choice for patients with chronic myeloid leukemia in chronic phase.

Intravenous Busulfan-Based Conditioning Prior to Allogeneic Stem Cell Transplantation in Adults Patients with AML - An ALWP-EBMT Survey.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1995-1995 ◽  
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Donald Bunjes ◽  
Pedro Pimentel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Disease ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
The Impact

Abstract Oral Busulfan (Bu) is the historical backbone of pre-allogeneic stem cell transplantation (alloSCT) conditioning regimen. However, oral Bu has an erratic and unpredictable absorption with wide inter and also intra-patient (pt) variability. In contrast, I.V. Busulfan (IV Bu) is with more predictable pharmacokinetics and favorable toxicity profile. In order to assess the impact of the use of IV Bu, the ALWP of the EBMT performed a survey in AML pts who received IV-Bu as part of their pre-alloSCT conditioning regimen. 36 EBMT centers participated in this study: 9 centers performed more than 10 transplants each. Overall, 271 alloSCT were analyzed. Age was 44 (range, 16–67) years. 146 were males (54%) and 125 (46%) were females. Disease status at alloSCT was CR1-53%, CR2-16%, primary refractory-13%, Rel1-12%, Rel2-5% and untreated-1%.77% of the pts were with intermediate, 15% with poor and 8% with good risk cytogenetics, respectively. Median WBC at diagnosis was 26×109/L. Conditioning consisted of IV Bu and cyclophosphamide (IV BuCy) in 52%, IV Bu and fludarabine (IV BuFlu) in 38% and various other IV Bu containing regimens in 10% of the pts, respectively. Overall, conditioning was myeloablative in 80% and reduced-intensity (RIC) in 20% of the alloSCT, respectively. Donors were: identical siblings-59%, matched unrelated-28%, mismatched unrelated-10%, mismatched family donors-2%, syngeneic 1%. 83% of the pts were transplanted with mobilized PBSC grafts while 17% received BM grafts. GVHD prophylaxis consisted of CSA and MTX in 85% of the transplants. With median follow up of 24 (range, 1–66) months, 53% of the pts are alive while 47% have died. Day 100 mortality was 7%. The incidence of veno-occlusive disease of the liver (VOD) was 10.4%. VOD was more frequent in pts that were transplanted from unrelated donors in comparison to those who were transplanted from sibling donors (18% vs. 5%, respectively). It was also more common after myeloablative conditioning than RIC (11.5% vs. 5.5%, respectively). Median age of pts with VOD was 42(17–65) years, not different than the age of the whole group, but they had more advanced disease (primary refrectory-35%, Rel2-30%). Day of onset of VOD was +10(range, 1–162). VOD was severe in only 15% of the pts and only 6 pts died of VOD. All together 30% of the pts with VOD are alive. Overall, alloSCT transplant related mortality (TRM) was 22±4% for pts transplanted at CR1 vs 33±8% for pts transplanted at advanced disease. Similarly, leukemia free survival (LFS) for pts transplanted at CR1 was 55±4% vs. 21+5% for pts transplanted in advanced disease. In summary, IV Bu based conditioning reduced the incidence and severity of VOD post alloSCT for AML as compared to published figures for historical controls. A randomized trial assessing VOD incidence and TRM using IV BuCy vs. IV BuFlu with 2 vs. 4 days of IV Bu, respectively may be indicated.

Outcome of HLA-Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation Depends On the Intensity of the Conditioning Regimen.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3393-3393
Author(s):  
Francis Ayuk ◽  
Tatjana Zabelina ◽  
Ulrike Bacher ◽  
Christine Wolschke ◽  
Heinrich Lellek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Conditioning Regimen ◽  
Patient Characteristics ◽  
Unrelated Donor ◽  
Hematopoetic Stem Cell ◽  
Unrelated Donors ◽  
Female Donor

Abstract Abstract 3393 Poster Board III-281 Background: HLA-mismatched unrelated donors are increasingly becoming a graft source for both standard myeloablative (MAC) and reduced intensity conditioning (RIC) hematopoetic stem cell transplantation (HSCT). Patients and methods: We retrospectively analysed the effects of HLA-mismatching in 553 patients undergoing MAC (n = 342) or RIC (n = 211) unrelated donor HLA-matched (n = 289) or -mismatched (n = 264) HSCT with antithymocyte globulin as part of conditioning. Patient characteristics well matched between HLA-matched and –mismatched groups of MAC and RIC patients. Results: Median follow-up was 1946 days for MAC patients and 765 days for RIC patients. In MAC patients, there was no difference in the incidence of aGvHD, treatment related mortality (TRM) and overall survival (OS) between recipients of HLA-matched vs. –mismatched allografts. In RIC patients on the contrary, the incidence of aGvHD II-IV (46%, vs. 32.0% p = 0.05), III-IV (18%, % vs. 9.0 p = 0.07) and TRM (35% vs. 20%, p = 0.04) were higher and OS lower (31% vs. 50%, p = 0.001) for recipients of HLA-mismatched vs. –matched transplants. In the RIC patients, female donor gender (RR: 1.8; p = 0.02) and HLA-mismatch (RR: 1.8; p = 0.02) negatively influenced TRM while female donor gender (RR: 1.58, p = 0.03), HLA-mismatch (RR: 1.82, p = 0.003) and bad risk disease (RR: 2.14, p < 0.001) negatively impacted OS. Conclusion: Our analyses surprisingly reveal that the positive effect of ATG in HLA-mismatched transplants is only limited to patients undergoing standard myeloablative conditioning. HLA-mismatching and female donor gender negatively impact outcome of RIC allogeneic unrelated donor HSCT despite the use of ATG, highlighting the need for improved strategies. Acknowledgments We thank the staff of the BMT unit for providing outstanding care to our patients and the medical technicians for their excellent work in the BMT laboratory. Disclosures: Off Label Use: Antithymocyte globulin for prevention of severe GVHD.

Differences of Antithymocyte Globulin (ATG) Side Effects during Allogeneic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5449-5449 ◽  
Author(s):  
Lucrecia Yañez San Segundo ◽  
Brenda Lopez Pereira ◽  
Maria Aranzazu Bermudez ◽  
Andres Insunza ◽  
Iñigo Romon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Conditioning Regimen ◽  
Platelet Recovery ◽  
Infusion Reactions ◽  
Cmv Reactivation

Abstract Introduction: Due to its production and mechanism of action, antithymocyte globulin (ATG) is associated with two main side effects: immunological responses and infections. Objective: We evaluate the incidence and differences of ATG infusion reactions and fungal and viral infections in patients who receive SCT across a period of 10 years. Patients and methods: From January 2005 to December 2014, 100 patients who underwent and allogeneic stem cell transplantation (SCT) in our center received ATG (Thymoglobulin [TG] or ATG-Fresenius [ATG-F]) as part of conditioning regimen. Because an out of trend had been noted in stability profiling of TG finished product lots manufactured since December 2009 and since July 2012, TG was switched by ATG-F, patients were divided into three groups (TG-1: 45 patients; TG-2: 31 patients; ATG-F: 24 patients). Total median dose of TG was 7.5 mg/Kg in both groups. Results: Patients transplanted with ATG-F were significantly older than those who received TG (p=0.009). In addition, the use of an unrelated donor and GVHD prophylaxis with calcineurin inhibitor combined with mycophenolate mofetil was more frequent in ATG-F group (p=0.04 and p <0.0001 respectively). There were no differences between the groups in the underlying disease and its status at the transplant, the intensity of the conditioning regimen and the recipient/donor CMV and EBV serology. The majority of patients engrafted (93.3%, 93.5% and 95.8%) and neutrophil and platelet recovery was similar between three groups. Although there were no statistical differences, TG-2 showed less acute and chronic GVHD compared with TG-1 and ATG-F. All patients received premedication with corticoids. In all groups, pyrexia and chills were the most frequent symptom associated with ATG administration. All patients in TG-2 group showed infusion reaction (p= 0.006) and compared with TG-1 and ATG-F, they presented more peripheral edema (p=0.003), diarrhea (p=0.001), pulmonary edema (p=0.002) and dyspnea (p=0.005). Fungal infection was more frequent in TG-1 (30.2% vs 13.3% and 4.3%,p=0.024). CMV reactivation and BK viruria was more frequent in ATG-F (p=0.048 and 0.005, respectively). In contrast, EBV reactivation and Post Transplant Lymphoproliferative Disorder (PTLD) was more frequent in TG-2 group (33.3% vs 2.6% and 16.7%, p=0.003 and 25.8% vs 0% and 4.2%, p<0.0001, respectively). Conclusion During ATG infusion, pyrexia and chills are the most common side in SCT. The screening and prophylaxis of fungal infections may be associated with the diminishing of the incidence of this complication during the studied period. The use of older patients and the mycophenolate may be associated with an increasing incidence of CMV reactivation. By contrast, it is unclear if the out of trend noted in stability profiling of TG finished product lots manufactured since December 2009 has had influence in the type of infusion reactions and the incidence of EBV reactivations and PTLD observed in the TG-2 group. Disclosures No relevant conflicts of interest to declare.

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