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P-218 Allogeneic stem cell transplantation in Argentina: Comparison between related and unrelated donors in adults with myelodysplastic syndrome
Poster Presentations – 12th International Symposium on Myelodysplastic Syndromes / Leukemia Research 37 S1 (2013) S1–S117
Purpose: To describe the kinetics of the cell chimerism and to analyze its impact on MDS/AML outcome patients after hematopoietic trasplant. Materials and Methods: 124 patients with MDS (n=56)/AML (n=68), allotransplanted in two different units from January 2005 to December 2012, were studied. Results: Median age at trasplant was 55 years and median CD34+ cell dose was 5.5×106 /kg. At day + 56, complete BM chimerism was present in 70% of patients while complete CD15 PB chimerism was 89% and complete CD3 PB chimerism was only 30%. At day +100 percentage of chimerism results was as follows: 74%, 92% and 40% of complete chimerism for BM, PB CD15 and PB CD3, respectively. All patients engrafted and at day +100, all alive patients but one (n=102) were in CR. MRD monitoring at day +100 was positive in 21% of patients. After a median follow up of 2 years, overall and relapse free survival were 57 and 60%, respectively. Regarding overall survival the presence of complete chimerism in BM at day +56 and +100 improves outcome (OS of 62% vs 51% and 64% vs 49% respectively at day +100 for patients with complete vs mixed chimerism, p=0.017 and p=0.02). When patients with mixed chimerism in BM at day +100 were analyzed for cGVHD development overall survival was improved for patients in which it was present (OS of 66% vs 28% for patients with and without cGVHD, p=0.02). Regarding relapse free survival (RFS) the presence of complete chimerism in BM at day +56 and +100 was associated with better evolution (RFS of 63% vs 60% at day +56 and 73% vs 60% at day +100 for patients with complete vs mixed chimerism, p=0.04 and p=0.004, respectively). Development of cGVHD in patients who showed mixed chimerism in BM at day +56 improved RFS in this subgroup of patients (RFS of 80% vs 33% for patients with and without cGVHD, p=0.03). Multivariate analysis for OS showed that the presence of MRD+ [HR 1.3 (0.08-0.8), p=0.02] and mixed BM chimerism at day +100 [HR 1.2 (0.09-0.9), p=0.04] were the two variables retaining statistical significance Conclusions: Early evaluation of chimerism may help to identify patients at high risk for relapse in AML/MDS.
P-217 Use of fludarabine and low dose intravenous busulfan as conditioning regimen in patients with Fanconi anemia and myelodysplastic syndromes B. George 1 , B. Poonkuzhali 1 , E.M. Pavai 1 , V. Mathews 1 , A. Srivastava 1 . 1 Haematology, Christian Medical College, Vellore, India Background: There is very limited data on the use of fludarabine and intravenous busulfan as conditioning regimen in patients with fanconi anemia and myelodysplastic syndrome. Introduction: Dose adjusted busulfan is associated with low toxicity. Purpose: Retrospective analysis of patients who underwent HSCT using a conditioning regimen of fludarabine and low dose intravenous Busulfan Materials and Methods: Between 2010 and 2012, 4 patients with Fanconi anemia (FA) and MDS underwent HLA identical sibling donor HSCT. Conditioning consisted of Fludarabine 30 mg/m2 /day x 6 days (day -7 to -2) and intravenous Busulfan (2.4 mg/kg/day x 2 days) days -3 and -2. Two patients received additional ATG (ATGAM 10 mg/kg/daily x 4 days). Graft source consisted of peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and low dose methotrexate. Results: Four males (aged 4, 7, 22 and 26 years) with FA and MDS underwent HSCT. Median time from diagnosis to HSCT was 45 months (range: 4-180). At diagnosis, 2 had bone marrow features of aplastic anemia while other two had hypoplastic MDS. At HSCT, two each had
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progressed to RCMD and MDS-RAEB1 respectively. Median Busulfan AUC levels were 3125 umoles (range: 2635–3585). Median cell dose infused was 7.8×106 CD34/kg (range: 4.1–12.9). All engrafted with a median time to ANC > 500/mm3 being 11 days (range: 10–13) and platelet count > 20,000/mm3 being 13 days (range: 12-16). Conditioning was well tolerated except for grade IV mucositis in 1 patient. None developed veno-occlusive disease of the liver. Grade II acute GVHD occurred in 1 patient while chronic extensive GVHD occurred in 2 patients (one following DLI for persistent mixed chimerism). All developed febrile neutropenia but none had documented bacterial or fungal infections. Two patients developed CMV reactivation on Days 30 and 46 post HSCT which responded well to ganciclovir. One patient relapsed as acute myeloid leukemia 26 months after HSCT despite having chronic extensive GVHD while other 3 are well 4, 6 and 12 months post HSCT. Conclusions: Conclusion: The use of fludarabine and low dose busulfan as a conditioning regimen for patients with FA and MDS is associated with good engraftment and low toxicity. Targeting a Busulfan AUC level of around 3000 umoles is associated with low toxicity. Larger studies need to be done to evaluate the role of this conditioning regimen in patients with FA and MDS.
P-218 Allogeneic stem cell transplantation in Argentina: Comparison between related and unrelated donors in adults with myelodysplastic syndrome A. Basquiera 1 , M.M. Rivas 2 , G. Remaggi 3 , J. Martínez Rolón 3 , R. Burgos 4 , V. Milovic 5 , J. Arbelbide 6 , C. Foncuberta 4 , J.H. Milone 7 , G. Jaimovich 8 , G. Kusminsky 2 , J.J. García 1 , M.V. Prates 7 . 1 Hematology and Oncology, Hospital Privado de Córdoba, Córdoba, Argentina; 2 Hematology, Hospital Austral, Buenos Aires, Argentina; 3 Transplantation Unit, Fundaleu, Buenos Aires, Argentina; 4 Bone Marrow Transplantation Unit, Instituto Alexander Fleming, Buenos Aires, Argentina; 5 Transplantation Unit, Hospital Alemán, Buenos Aires, Argentina; 6 Hematology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 7 Bone Marrow Transplantation Unit, Hospital Italiano de La Plata, La Plata, Argentina; 8 Transplantation Unit, Fundación Favaloro, Buenos Aires, Argentina Background: Allogeneic stem cell transplantation (SCT) in patients with myelodysplastic syndrome (MDS) is a curative treatment approach. However, only 30% of patients have a related donor, so for the rest of patients an unrelated donor is required. Introduction: Non-relapse mortality (NRM) and graft versus host disease (GVHD) are still concerns in unrelated donor SCT setting. Purpose: Our objective was to compare the clinical outcome between related and unrelated donors in terms of progression free survival (PFS), overall survival (OS), and relapse and NRM. Materials and Methods: In this multicenter retrospective study, we analyzed data from 76 adults with MDS who underwent SCT at eight centers in Argentina between 1995 and 2012. Results: A total of 76 patients (mean of age=42 years; range=18-66) underwent allogeneic SCT after treatment with a myeloablative conditioning (n=50) or a non-myeloablative conditioning (n=26). Unmanipulated G-CSF mobilized peripheral blood stem cells (n=57) or bone marrow cells (n=19) were transplanted from related (n=53) or unrelated (n=23) donors. Most patients (50/76, 65.8%) had advanced MDS at diagnosis, and 10/76 (13.1%) were secondary MDS. Clinical and procedure-related characteristics between related and unrelated donor transplants were comparable except for a shorter time since diagnosis to transplantation in related vs. unrelated donors (median of time 7.2 vs. 14.7 months, respectively; p=0.001). Median of followup of the surviving cohort was 72.7 months in related vs. 12.1 months in unrelated donor recipients (p=0.01). For all patients, unadjusted 5-year PFS and OS was 35.2% and 38.5% respectively; no significant
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Poster Presentations – 12th International Symposium on Myelodysplastic Syndromes / Leukemia Research 37 S1 (2013) S1–S117
difference was found between related and unrelated donor recipients. Cumulative incidence (CI) of NRM was 27.5%, and 7%, 10.5%, 17.3% and 23.8% at 30 days, 100 days, one year and two years, respectively. CI of relapse was 42.4%, and 0%, 4%, 28.6% and 35.2% at 30 days, 100 days, one year and two years, respectively. No difference between related and unrelated donors was observed in CI of NRM (26.5% vs. 26.1%) neither in CI of relapse (41.5% vs. 42.3%). In multivariate Cox analysis, chronic GVHD was associated with better PFS (adjusted HR=0.26; 0.09-0.79; p=0.02) and better OS (adjusted HR=0.27; 0.09-0.78; p=0.01) including age, conditioning regimen, disease status pre-transplantation, stem cell source, donor, and acute and chronic GVHD. Conclusions: In our country, allogeneic SCT using unrelated donors is feasible and has, at least, similar outcome compared to related donors. Long term survival was achieved in more than 30% of the patients.
P-219 T cell depleted (TCD) allogeneic hematopoietic stem cell transplant for older patients with advanced MDS and AML evolved from MDS R. Tamari 1 , S. Chung 2 , S. Devlin 3 , A. Jakubowski 1 , E. Papadopoulos 1 , M.A. Perales 1 , D. Ponce 1 , J. Goldberg 1 , J. Barker 1 , C. Sauter 1 , G. Koehne 1 , J. Young 1 , S. Giralt 1 , H. Castro-Malaspina 1 . 1 Medicine Adult Bone Marrow Transplant, Memorial Sloan-Kettering Cancer Center, New York, USA; 2 Medicine Leukemia, Memorial Sloan-Kettering Cancer Center, New York, USA; 3 Bio-statistics, Memorial Sloan-Kettering Cancer Center, New York, USA Background: MDS are a group of diseases of the elderly. Allo-HSCT is the only curative treatment for advanced MDS (RAEB-1 and higher). Its use in older patients became possible with the development of reduced intensity conditioning (RIC). Introduction: Although RIC allo-HSCT seems to provide a survival advantage when compared to supportive care, it carries the risk of transplant-related mortality due in great part to GvHD. Purpose: To assess the outcomes of TCD allo-HSCT in patients ≥50 years old with advanced MDS and AML evolved from MDS. Materials and Methods: Between 1985-2011, 105 pts age ≥50 underwent TCD HSCT. Median age was 58 (88 pts were 50-64 & 17 ≥ 65). Donors were MRD: 50, MURD: 35 and mismatched related or unrelated: 20. Conditioning regimens included TBI based: 31& busulphan-based: 74. ATG was given to prevent graft rejection. The highest disease status by WHO criteria were: RAEB-1: 14, RAEB-2: 30, and AML: 54. Chromosomal abnormalities were present in 51 pts; 25 were poor risk as per IPSS. Eighty-four pts received chemotherapy before conditioning: 60 intensive chemotherapy, 12 hypomethylating agents and 12 both. At transplant 44 pts were in hematologic CR, 41 in second refractory cytopenia, 19 in RAEB 1 & 2, and 1 pt with AML. 22 had persistent chromosomal abnormalities, 10 with poor risk per IPSS. BM grafts (21) were depleted of T-cells using soybean agglutinin and then sheep RBC rosetting; PBSC grafts (84) by using immunomagnetic CD34+ selection (Isolex initially & CliniMACS after 09/2011). No post-transplant prophylaxis for GvHD was given. Results: Ninety-eight % of pts engrafted; two died before engraftment (2%) and two developed late graft failure. The cumulative incidence (CI) with 95% confidence interval of grade II-IV aGVHD at day180 was 14% (8%-22%) & at 1-year 18% (11%-26%). The CI of cGVHD at 2-year was 3% (0.8%-8%). OS at 2 years was 57% (47%-68%) & at 5 years 44% (35%-55%). The DFS at 2 years was 52% (43%-64%) & at 5 years 42% (33%-53%). The CI of NRM at day 100 was 9% (4%-15%), at 1 year 25% (17%-34%) and at 2 years 33% (24%-42%). The CI of relapse at 1 year was 12% (7%-20%) & at 2 years 17% (CI 10%-24%). The OS, DFS, NRM & relapse rates were not statistically significant in the 2 subgroups of older pts (50-64 & >65).
Conclusions: Older pts with advanced MDS can achieve durable remissions and long-term survival with TCD HSCT. Despite requiring more intensive conditioning regimens, these pts tolerated them well and the outcomes seem comparable to those of unmodified alloHSCT, although with a much lower incidence of GVHD.
P-220 A comparison of effect of stem cell transplantation (SCT) with different treatment approaches on long term survival of MDS patients J. Cermak 1 , A. Vitek 1 , D. Mikulenkova 1 , M. Lukasova 1 , K. Michalova 2 , J. Brezinova 2 , M. Markova-Stastna 1 , P. Cetkovsky 1 . 1 Clinical Hematology, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic; 2 Cytogenetics, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic Introduction: Allogeneic SCT is still considered the only curative treatment in MDS. A long term follow up has been studied in patients from a single center registry. Purpose: The purpose of the study was to compare effect of SCT with other treatment options. Materials and Methods: An analysis included 335 patients with primary MDS treated in the years 1981–2010. Results: Allogeneic SCT was performed in 37 patients with MDS with ≤ 5% of bone marrow (BM) blasts, a comparison with similar cohort of 128 patients treated with supportive care only (SC) revealed no difference in median survival (84,2 months for SCT v.s. 88,5 months for SC). Estimated 1 and 3 years survival were similar, however, a significant difference was observed in estimated 5 years survival (62.2% for SCT v.s. 40.6% for SC) and 10 years survival (51,4% for SCT v.s. 25.8% for SC). The reason was a significant rate of progression (28.9%) and comorbidities related death (19.5%) in SC group. In patients with > 10% of BM blasts, SCT was the only effective treatment in 27 patients with estimated 3, 5 and 10 years survival of 63.0, 55.6 and 51.2%, respectively. Median survival of SCT patients was 71.4 months compared to only 12.5 months in 79 non-transplanted patients, where estimated 3 years survival was 14.3% for low dose ARA-C and 18.2% for hypomethylating agents and none of the patients treated with combination chemotherapy only survived > 31 months. Estimated 10 years survival of patients who were transplanted with ≥ 10% BM blasts at the time of conditioning was only 22.2% and 33.3% v.s. 66.7% with and 22.0% in those transplanted with < 10% BM blasts. Median survival of transplanted patients with 6-10% of BM blasts was 44.1 months compared to 11.8 months for other types of treatment. However, estimated 3 years survival after SCT was in this subgroup only 36.8% mainly because of high rate of transplantation related mortality due to poor and complicated engraftment. Conclusions: The results suggest that MDS RAEB I. represent MDS subgroup with less optimal response to intensive treatment than patients with more advanced disease, where our results were comparable with those in de novo AML patients. A long term preceeding profound disorder of hematopoiesis including BM environment might be a possible explanation for poor response of MDS RAEB I. patients to treatment and new drugs, eg. hypomethylating agents should be introduced also in this subgroup.
P-221 Characteristic of relapse after T cell depleted (TCD) allogeneic hematopoietic stem cell transplantation in patients with advanced MDS R. Tamari 1 , S. Chung 2 , S. Devlin 3 , A. Jakubowski 1 , E. Papadopoulos 1 , F. Boulad 4 , T. Small 4 , N. Kernan 4 , D. Ponce 1 , C. Sauter 1 , J. Young 1 , S. Giralt 1 , R. O’Reilly 4 , H. Castro-Malaspina 1 . 1 Medicine Adult Bone
Purpose: To describe the kinetics of the cell chimerism and to analyze its impact on MDS/AML outcome patients after hematopoietic trasplant. Materials and Methods: 124 patients with MDS (n=56)/AML (n=68), allotransplanted in two different units from January 2005 to December 2012, were studied. Results: Median age at trasplant was 55 years and median CD34+ cell dose was 5.5×106 /kg. At day + 56, complete BM chimerism was present in 70% of patients while complete CD15 PB chimerism was 89% and complete CD3 PB chimerism was only 30%. At day +100 percentage of chimerism results was as follows: 74%, 92% and 40% of complete chimerism for BM, PB CD15 and PB CD3, respectively. All patients engrafted and at day +100, all alive patients but one (n=102) were in CR. MRD monitoring at day +100 was positive in 21% of patients. After a median follow up of 2 years, overall and relapse free survival were 57 and 60%, respectively. Regarding overall survival the presence of complete chimerism in BM at day +56 and +100 improves outcome (OS of 62% vs 51% and 64% vs 49% respectively at day +100 for patients with complete vs mixed chimerism, p=0.017 and p=0.02). When patients with mixed chimerism in BM at day +100 were analyzed for cGVHD development overall survival was improved for patients in which it was present (OS of 66% vs 28% for patients with and without cGVHD, p=0.02). Regarding relapse free survival (RFS) the presence of complete chimerism in BM at day +56 and +100 was associated with better evolution (RFS of 63% vs 60% at day +56 and 73% vs 60% at day +100 for patients with complete vs mixed chimerism, p=0.04 and p=0.004, respectively). Development of cGVHD in patients who showed mixed chimerism in BM at day +56 improved RFS in this subgroup of patients (RFS of 80% vs 33% for patients with and without cGVHD, p=0.03). Multivariate analysis for OS showed that the presence of MRD+ [HR 1.3 (0.08-0.8), p=0.02] and mixed BM chimerism at day +100 [HR 1.2 (0.09-0.9), p=0.04] were the two variables retaining statistical significance Conclusions: Early evaluation of chimerism may help to identify patients at high risk for relapse in AML/MDS.
P-217 Use of fludarabine and low dose intravenous busulfan as conditioning regimen in patients with Fanconi anemia and myelodysplastic syndromes B. George 1 , B. Poonkuzhali 1 , E.M. Pavai 1 , V. Mathews 1 , A. Srivastava 1 . 1 Haematology, Christian Medical College, Vellore, India Background: There is very limited data on the use of fludarabine and intravenous busulfan as conditioning regimen in patients with fanconi anemia and myelodysplastic syndrome. Introduction: Dose adjusted busulfan is associated with low toxicity. Purpose: Retrospective analysis of patients who underwent HSCT using a conditioning regimen of fludarabine and low dose intravenous Busulfan Materials and Methods: Between 2010 and 2012, 4 patients with Fanconi anemia (FA) and MDS underwent HLA identical sibling donor HSCT. Conditioning consisted of Fludarabine 30 mg/m2 /day x 6 days (day -7 to -2) and intravenous Busulfan (2.4 mg/kg/day x 2 days) days -3 and -2. Two patients received additional ATG (ATGAM 10 mg/kg/daily x 4 days). Graft source consisted of peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and low dose methotrexate. Results: Four males (aged 4, 7, 22 and 26 years) with FA and MDS underwent HSCT. Median time from diagnosis to HSCT was 45 months (range: 4-180). At diagnosis, 2 had bone marrow features of aplastic anemia while other two had hypoplastic MDS. At HSCT, two each had
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progressed to RCMD and MDS-RAEB1 respectively. Median Busulfan AUC levels were 3125 umoles (range: 2635–3585). Median cell dose infused was 7.8×106 CD34/kg (range: 4.1–12.9). All engrafted with a median time to ANC > 500/mm3 being 11 days (range: 10–13) and platelet count > 20,000/mm3 being 13 days (range: 12-16). Conditioning was well tolerated except for grade IV mucositis in 1 patient. None developed veno-occlusive disease of the liver. Grade II acute GVHD occurred in 1 patient while chronic extensive GVHD occurred in 2 patients (one following DLI for persistent mixed chimerism). All developed febrile neutropenia but none had documented bacterial or fungal infections. Two patients developed CMV reactivation on Days 30 and 46 post HSCT which responded well to ganciclovir. One patient relapsed as acute myeloid leukemia 26 months after HSCT despite having chronic extensive GVHD while other 3 are well 4, 6 and 12 months post HSCT. Conclusions: Conclusion: The use of fludarabine and low dose busulfan as a conditioning regimen for patients with FA and MDS is associated with good engraftment and low toxicity. Targeting a Busulfan AUC level of around 3000 umoles is associated with low toxicity. Larger studies need to be done to evaluate the role of this conditioning regimen in patients with FA and MDS.
P-218 Allogeneic stem cell transplantation in Argentina: Comparison between related and unrelated donors in adults with myelodysplastic syndrome A. Basquiera 1 , M.M. Rivas 2 , G. Remaggi 3 , J. Martínez Rolón 3 , R. Burgos 4 , V. Milovic 5 , J. Arbelbide 6 , C. Foncuberta 4 , J.H. Milone 7 , G. Jaimovich 8 , G. Kusminsky 2 , J.J. García 1 , M.V. Prates 7 . 1 Hematology and Oncology, Hospital Privado de Córdoba, Córdoba, Argentina; 2 Hematology, Hospital Austral, Buenos Aires, Argentina; 3 Transplantation Unit, Fundaleu, Buenos Aires, Argentina; 4 Bone Marrow Transplantation Unit, Instituto Alexander Fleming, Buenos Aires, Argentina; 5 Transplantation Unit, Hospital Alemán, Buenos Aires, Argentina; 6 Hematology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 7 Bone Marrow Transplantation Unit, Hospital Italiano de La Plata, La Plata, Argentina; 8 Transplantation Unit, Fundación Favaloro, Buenos Aires, Argentina Background: Allogeneic stem cell transplantation (SCT) in patients with myelodysplastic syndrome (MDS) is a curative treatment approach. However, only 30% of patients have a related donor, so for the rest of patients an unrelated donor is required. Introduction: Non-relapse mortality (NRM) and graft versus host disease (GVHD) are still concerns in unrelated donor SCT setting. Purpose: Our objective was to compare the clinical outcome between related and unrelated donors in terms of progression free survival (PFS), overall survival (OS), and relapse and NRM. Materials and Methods: In this multicenter retrospective study, we analyzed data from 76 adults with MDS who underwent SCT at eight centers in Argentina between 1995 and 2012. Results: A total of 76 patients (mean of age=42 years; range=18-66) underwent allogeneic SCT after treatment with a myeloablative conditioning (n=50) or a non-myeloablative conditioning (n=26). Unmanipulated G-CSF mobilized peripheral blood stem cells (n=57) or bone marrow cells (n=19) were transplanted from related (n=53) or unrelated (n=23) donors. Most patients (50/76, 65.8%) had advanced MDS at diagnosis, and 10/76 (13.1%) were secondary MDS. Clinical and procedure-related characteristics between related and unrelated donor transplants were comparable except for a shorter time since diagnosis to transplantation in related vs. unrelated donors (median of time 7.2 vs. 14.7 months, respectively; p=0.001). Median of followup of the surviving cohort was 72.7 months in related vs. 12.1 months in unrelated donor recipients (p=0.01). For all patients, unadjusted 5-year PFS and OS was 35.2% and 38.5% respectively; no significant
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Poster Presentations – 12th International Symposium on Myelodysplastic Syndromes / Leukemia Research 37 S1 (2013) S1–S117
difference was found between related and unrelated donor recipients. Cumulative incidence (CI) of NRM was 27.5%, and 7%, 10.5%, 17.3% and 23.8% at 30 days, 100 days, one year and two years, respectively. CI of relapse was 42.4%, and 0%, 4%, 28.6% and 35.2% at 30 days, 100 days, one year and two years, respectively. No difference between related and unrelated donors was observed in CI of NRM (26.5% vs. 26.1%) neither in CI of relapse (41.5% vs. 42.3%). In multivariate Cox analysis, chronic GVHD was associated with better PFS (adjusted HR=0.26; 0.09-0.79; p=0.02) and better OS (adjusted HR=0.27; 0.09-0.78; p=0.01) including age, conditioning regimen, disease status pre-transplantation, stem cell source, donor, and acute and chronic GVHD. Conclusions: In our country, allogeneic SCT using unrelated donors is feasible and has, at least, similar outcome compared to related donors. Long term survival was achieved in more than 30% of the patients.
P-219 T cell depleted (TCD) allogeneic hematopoietic stem cell transplant for older patients with advanced MDS and AML evolved from MDS R. Tamari 1 , S. Chung 2 , S. Devlin 3 , A. Jakubowski 1 , E. Papadopoulos 1 , M.A. Perales 1 , D. Ponce 1 , J. Goldberg 1 , J. Barker 1 , C. Sauter 1 , G. Koehne 1 , J. Young 1 , S. Giralt 1 , H. Castro-Malaspina 1 . 1 Medicine Adult Bone Marrow Transplant, Memorial Sloan-Kettering Cancer Center, New York, USA; 2 Medicine Leukemia, Memorial Sloan-Kettering Cancer Center, New York, USA; 3 Bio-statistics, Memorial Sloan-Kettering Cancer Center, New York, USA Background: MDS are a group of diseases of the elderly. Allo-HSCT is the only curative treatment for advanced MDS (RAEB-1 and higher). Its use in older patients became possible with the development of reduced intensity conditioning (RIC). Introduction: Although RIC allo-HSCT seems to provide a survival advantage when compared to supportive care, it carries the risk of transplant-related mortality due in great part to GvHD. Purpose: To assess the outcomes of TCD allo-HSCT in patients ≥50 years old with advanced MDS and AML evolved from MDS. Materials and Methods: Between 1985-2011, 105 pts age ≥50 underwent TCD HSCT. Median age was 58 (88 pts were 50-64 & 17 ≥ 65). Donors were MRD: 50, MURD: 35 and mismatched related or unrelated: 20. Conditioning regimens included TBI based: 31& busulphan-based: 74. ATG was given to prevent graft rejection. The highest disease status by WHO criteria were: RAEB-1: 14, RAEB-2: 30, and AML: 54. Chromosomal abnormalities were present in 51 pts; 25 were poor risk as per IPSS. Eighty-four pts received chemotherapy before conditioning: 60 intensive chemotherapy, 12 hypomethylating agents and 12 both. At transplant 44 pts were in hematologic CR, 41 in second refractory cytopenia, 19 in RAEB 1 & 2, and 1 pt with AML. 22 had persistent chromosomal abnormalities, 10 with poor risk per IPSS. BM grafts (21) were depleted of T-cells using soybean agglutinin and then sheep RBC rosetting; PBSC grafts (84) by using immunomagnetic CD34+ selection (Isolex initially & CliniMACS after 09/2011). No post-transplant prophylaxis for GvHD was given. Results: Ninety-eight % of pts engrafted; two died before engraftment (2%) and two developed late graft failure. The cumulative incidence (CI) with 95% confidence interval of grade II-IV aGVHD at day180 was 14% (8%-22%) & at 1-year 18% (11%-26%). The CI of cGVHD at 2-year was 3% (0.8%-8%). OS at 2 years was 57% (47%-68%) & at 5 years 44% (35%-55%). The DFS at 2 years was 52% (43%-64%) & at 5 years 42% (33%-53%). The CI of NRM at day 100 was 9% (4%-15%), at 1 year 25% (17%-34%) and at 2 years 33% (24%-42%). The CI of relapse at 1 year was 12% (7%-20%) & at 2 years 17% (CI 10%-24%). The OS, DFS, NRM & relapse rates were not statistically significant in the 2 subgroups of older pts (50-64 & >65).
Conclusions: Older pts with advanced MDS can achieve durable remissions and long-term survival with TCD HSCT. Despite requiring more intensive conditioning regimens, these pts tolerated them well and the outcomes seem comparable to those of unmodified alloHSCT, although with a much lower incidence of GVHD.
P-220 A comparison of effect of stem cell transplantation (SCT) with different treatment approaches on long term survival of MDS patients J. Cermak 1 , A. Vitek 1 , D. Mikulenkova 1 , M. Lukasova 1 , K. Michalova 2 , J. Brezinova 2 , M. Markova-Stastna 1 , P. Cetkovsky 1 . 1 Clinical Hematology, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic; 2 Cytogenetics, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic Introduction: Allogeneic SCT is still considered the only curative treatment in MDS. A long term follow up has been studied in patients from a single center registry. Purpose: The purpose of the study was to compare effect of SCT with other treatment options. Materials and Methods: An analysis included 335 patients with primary MDS treated in the years 1981–2010. Results: Allogeneic SCT was performed in 37 patients with MDS with ≤ 5% of bone marrow (BM) blasts, a comparison with similar cohort of 128 patients treated with supportive care only (SC) revealed no difference in median survival (84,2 months for SCT v.s. 88,5 months for SC). Estimated 1 and 3 years survival were similar, however, a significant difference was observed in estimated 5 years survival (62.2% for SCT v.s. 40.6% for SC) and 10 years survival (51,4% for SCT v.s. 25.8% for SC). The reason was a significant rate of progression (28.9%) and comorbidities related death (19.5%) in SC group. In patients with > 10% of BM blasts, SCT was the only effective treatment in 27 patients with estimated 3, 5 and 10 years survival of 63.0, 55.6 and 51.2%, respectively. Median survival of SCT patients was 71.4 months compared to only 12.5 months in 79 non-transplanted patients, where estimated 3 years survival was 14.3% for low dose ARA-C and 18.2% for hypomethylating agents and none of the patients treated with combination chemotherapy only survived > 31 months. Estimated 10 years survival of patients who were transplanted with ≥ 10% BM blasts at the time of conditioning was only 22.2% and 33.3% v.s. 66.7% with and 22.0% in those transplanted with < 10% BM blasts. Median survival of transplanted patients with 6-10% of BM blasts was 44.1 months compared to 11.8 months for other types of treatment. However, estimated 3 years survival after SCT was in this subgroup only 36.8% mainly because of high rate of transplantation related mortality due to poor and complicated engraftment. Conclusions: The results suggest that MDS RAEB I. represent MDS subgroup with less optimal response to intensive treatment than patients with more advanced disease, where our results were comparable with those in de novo AML patients. A long term preceeding profound disorder of hematopoiesis including BM environment might be a possible explanation for poor response of MDS RAEB I. patients to treatment and new drugs, eg. hypomethylating agents should be introduced also in this subgroup.
P-221 Characteristic of relapse after T cell depleted (TCD) allogeneic hematopoietic stem cell transplantation in patients with advanced MDS R. Tamari 1 , S. Chung 2 , S. Devlin 3 , A. Jakubowski 1 , E. Papadopoulos 1 , F. Boulad 4 , T. Small 4 , N. Kernan 4 , D. Ponce 1 , C. Sauter 1 , J. Young 1 , S. Giralt 1 , R. O’Reilly 4 , H. Castro-Malaspina 1 . 1 Medicine Adult Bone