Outcome of Allogeneic Stem Cell Transplantation for Patients with Severe Aplastic Anemia after Conditioning with Procarbazine, ATG and Cyclophosphamide: A Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2027-2027
Author(s):  
Ki Seong ◽  
Jong Wook Lee ◽  
Yoo Jin Kim ◽  
Hee Je Kim ◽  
Chang Ki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Platelet Recovery ◽  
Matched Sibling

Abstract Background: Cyclophosphamide (CY, 200 mg/kg) plus ATG seems to be accepted as a standard conditioning regimen in HLA-matched sibling stem cell transplantation (SCT) for severe aplastic anemia (SAA). We report herein the outcome of allogeneic SCT for the patients with SAA conditioned with procarbazine (PCB), ATG and CY. Methods: Between January 1995 and March 2004, consecutive one hundred and sixty two patients with SAA received matched sibling SCT after conditioning with PCB, ATG and CY. The median age of patients was 28.5 (16~50) and median interval between diagnosis and SCT was 10.5 months (1~216). Fifty-five patients (34%) had a history of immunosuppressive therapy before SCT. The conditioning regimen consisted of PCB (6.25 mg/kg/day, 6 days), CY (50 mg/kg/day, 4 days) and ATG (1.25 mg/kg/day, 3 days). No graft manipulation was performed in 92 patients (52%), and donor marrow expansion and megadose transplantation (bone marrow plus CD34+ isolated PB as a stem cell source) were done in 35 patients (21.6%). All patients received of cyclosporine and methotrexate as GVHD prophylaxis. Results: The median dose of CD34+ and CD3+ cells infused were 4.8 x 106/kg (0.8~49.6) and 5.1 x 107/kg (0 ~ 38), respectively. Median time to neutrophil recovery more than 500/μL and platelet recovery more than 20,000/μL were 13 days (0~49) and 19 days (0~150), respectively. All patients achieved successful primary engraftment, but delayed engraftment failure developed in 18 patients (11%). Ten among 18 patients who developed graft failure received second SCT, resulting survival of 9 patients. The incidence of acute (more than grade II) and chronic GVHD were 9.3% (n=15) and 13.0 % (n=21), respectively. DFS and overall survival (OS) at 6 years was also 90%. Factors influencing on DFS on univariate analysis were patient and donor’s age, development of acute and chronic GVHD, and times of pregnancy (over 2 times). Development of acute and chronic GVHD, and occurrence of rejection were factors that influence DFS on multivariate analysis. Causes of death (n=15) were pneumonia (n=4), rejection (n=4), GVHD±infection (n=2), chronic GVHD (n=1), MOF (n=1), CVA (n=1), autoimmune hemolytic anemia (n=1), and unknown (n=1). Conclusions: These data suggest that the conditioning regimen used in this study is feasible for patients with SAA who received matched sibling SCT. GVHD and rejection were the most important factors that influence DFS.

HLA-Matched Sibling Stem Cell Transplantation Using Conditioning Regimen with Reduced Dose of Cyclophosphamide, ATG and Fludarabine in Patients with Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3296-3296
Author(s):  
Jong Wook Lee ◽  
Byung Sik Cho ◽  
Yoo Jin Kim ◽  
Seok Lee ◽  
Hee Je Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Cardiac Toxicity ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Matched Sibling

Abstract Background: We have reported the outcome of HLA-matched stem cell transplantation (SCT) using triple immunosuppressive agents with cyclophosphamide (CY, 200mg/kg), ATG and procarbazine for 113 adult patients with severe aplastic anemia (SAA) (Kim et al, BMT31:79, 2003). However, high dose CY (200mg/kg) causes serious cardiac toxicity in some cases which may lead to death within few weeks. To avoid high dose CY-associated cardiac toxicity we underwent HLA-matched sibling SCT using increasing dose of ATG and Fludarabine instead of reduced CY to half dose. Method: Between March 2002 and December 2007, fifty patients with adult SAA (six patients were AA/PNH syndrome) received matched sibling SCT. The median age of patients was 39 (16~53) and median interval between Dx and SCT was 19 months (1~352). The median number of transfusion prior to SCT was 34 units (2~680). Nineteen patients (38%) had a history of IST before SCT. The conditioning regimen consisted of Fludarabine (30mg/m2/day, 6 days), CY (50 mg/kg/day, 2 days) and ATG (Thymoglobulin 2.5mg/kg/day, 4 days). Stem cell sources were BM plus CD34+-selected PBSC (n=12), BM (n=20), PBSC (n=4) and G-CSF-primed BM (n=14). All patients received cyclosporine and methotrexate as GVHD prophylaxis. Results: The median dose of CD34+ cells infused was 3.7x106/kg (1.2~11.9). All patients achieved successful primary engraftment, and the median time for ANC and platelet to reach 0.5x109/L and 20x109/L was 12 (10~19) and 17 (10~25) days, respectively. Three patients (6%) developed delayed graft failure whereas 14% (16 out of 113) developed both primary and secondary graft failure in our previous study. But all achieved successful engraftment after booster infusion (n=1) and second SCT (n=2). The incidence of acute GVHD (more than grade II) and chronic GVHD was 8% (n=4) and 4% (n=2; extensive type), respectively. The incidence of acute and chronic GVHD seems to be lower than those of previous conditioning regimen (11% and 12%, respectively) (BMT31:79, 2003). The incidence of CMV infection requiring preemptive treatment was 54 % (n=27). Three patients died of reactivation of chronic hepatitis C with hepatic GVHD (n=1), CMV pneumonia (n=1), and invasive fungal infection (n=1). PNH clone monitored by flow cytometry disappeared posttransplant in all 6 PNH patients. With median follow up of 32 months (1~74), the estimated probability of survival at 3 years was 94 % compared with those of 89% in our previous report. Conclusions: These data demonstrate that the conditioning regimen used in this study is feasible for patients with SAA who received matched sibling SCT. Of note, the observation of successful engraftment as well as lesser acute and chronic GVHD compared with previous study suggest that increasing dose of ATG and the addition of Fludarabine has potent in vivo T cell depletion and immunomodulatory activity.

More Intensity Immuno-Suppression In Conditioning Regimen  may Favor Donor Stem Cell Sustained Engraftment In Allogeneic Stem Cell Transplantation For Acquired Severe Aplastic Anemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5452-5452
Author(s):  
Sun Can ◽  
Lin Xia ◽  
Huang Yuxian ◽  
Chen Tuzhen ◽  
Bingyi Wu
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Acquired Severe Aplastic Anemia

Abstract Background Hematopoietic stem cell transplantation (HSCT) is the first-line therapy for patients younger less than 40 years old with severe aplastic anemia (SAA). And the long-term survival for patients with SAA who received HSCT reaches to 70%-90%. Cyclophosphamide-based conditioning regimen with or without antithymocyte globulin (ATG) has been adopted in majority of HSCT for SAA patients with HLA matched related donor. However the graft rejection and graft failure in HSCT for SAA with cyclophosphamide-based conditioning regimen is still as high as 5%-16%. The aim of this study is to explore whether more immue suppression in conditioning regimen could favor the donor stem cells sustained engraftment for severe aplastic anemia patients receiving allogeneic hematopoietic stem cell transplantation. Fludarabine and busulfan were added in cyclophosphamide-based conditioning regimen to intensity immune suppression in conditioning. Methods To analyze the outcomes and chimeras of 40 patients with SAA who received HLA matched allo-HSCT from 2000 to 2012 with either fludarabine-based conditioning regimen or cyclophosphamide-based conditioning regimen retrospectively and to explore the relationship between the chimeras and conditioning regimen. Results Forty patients with SAA who received HLA matched allo-HSCT From May, 2000 to Dec. 2012. Twelve patients ( median age 25 year old  range 13-52, male 7, femal 5) received  fludarabine-based conditioning regimen which composed of fludarabine (30 mg/m2/d ×5d), busulfan ( 3 mg/kg ×2d ), cyclophosphamide ( 60mg/kg/d×2d) and ATG (2.5mg/kg/d ×5d). Twenty patients( median age 23 year old  range 12-42, male 19, femal 9)  received  cyclophosphamide-based conditioning regimen which composed of cyclophosphamide (50mg/kg/d ×4d )and ATG (2.5mg/kg/d ×2d ). The  median dose of MNC were 4.5×108/kg (range 3.8-7.0×108/kg )and 3.58×108/kg (range 3.2-6.8×108/kg ) and CD34+ cells were  4.5×108/kg and 3.58×108/kg respectively. GVHD prophylaxis were cyclosporine and short-term course methotrexate. Donor chimera was detected on day+30, +90, +180, and 360 after HSCT by short tandem repeat polymerase chain reaction, or fluorescein in situ hybridization for X and Y chromosomes in cases when patients and donors were sex mismatched. Results All patients with fludarabine-based conditioning regimen were successful Hematopoietic reconstitution and no graft failure occurred in this group patients. But two patients could not get recovery in cyclophosphamid-based conditioning regimen group. And complete donor chimeras always present when chimeras were detected by STR-PCR or FISH at day 30,day 60, day 90 and d 180 post transplantation in fludarabine-based conditioning regimen group, while seven patients with cyclophosphamide-based conditioning regimen were mixed chimeras at day 30 post transplant.  The graft was rejected in six of the seven patients at day 90 post transplant in cyclophosphamide-based conditioning regimen group. The complete donor chimera in fludarabine-based conditioning regimen group was obvious higher than that in cyclophosphamide-based conditioning regimen group ( p=0.037). The incidence of aGVHD in the fludarabine group was 16.7% and 10.7% in the cyclophosphamide-based group. There is no significant difference of aGVHD between two group (P = 0.627). The incidence of cGVHD was 8.3% and 10.7% respectively. The bacterial infections developed in 16.7% and 28.6% of patients respectively (P=0.693), The overall survival were 83.33% and 82.14% in fludarabine-based conditioning regimen group and cyclophosphamide-based group respectively (p=0.870). Conclusions More intensity immuno-suppression in conditioning regimen may favor donor stem cell sustained engraftment in allogeneic stem cell transplantation for acquired severe aplastic anemia patients. Disclosures: No relevant conflicts of interest to declare.

Similar Outcomes of Allogeneic Hematopoietic Cell Transplantation from Matched Sibling Donor and Haploidentical Donor for Refractory/Relapsed Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5511-5511
Author(s):  
Dai-Hong Liu ◽  
Li Yu ◽  
Wenrong Huang ◽  
Liping Dou ◽  
Honghua Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Sibling Donor ◽  
Matched Sibling

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only effective, even curative treatment for refractory/relapsed AML patients. Unmanipulated haploidentical HCT (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Unmanipulated haplo-HCT from G-CSF mobilized bone marrow and peripheral blood stem cell (PBSC) has shown similar results as that from MSD-HCT in leukemia. Here, we report the results of a cohort study on the efficacy and toxicity of haplo-PBSCT compared with MSD-PBSCT for treatment of refractory/relapsed AML. PATIENTS AND METHODS Among 419 newly diagnosed AML patients, 69 patients relapsed during CR1 and were planned to receive allo-HCT after re-induction. The order of preference of donors was MSD, matched unrelated (HLA 10/10 or 9/10 loci matched), or haploidentical donor. Thirty patients received haplo-PBSCT and 13 patients MSD-HCT (July, 2007 ~ June, 2014) at our unit. There was no difference of the characteristics of demography, disease or transplantation between these two groups (Table 1). High-resolution DNA techniques were used to evaluate the HLA-A, B, DRB1, DQB1, and C loci. Donors were treated with rhG-CSF (5 mg.kg-1.day-1) for consecutive days. The PBSCs were collected on day 5 - 6 and infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, intravenously, days -10 ~ -8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7 ~ -6), CY (120 mg kg-1, days -4 ~ -3), and ATG (rabbit; 10 mg.kg-1, days -5 ~ -2). MSD-HCT patients had the same conditioning regimen without ATG. All transplant recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was June 30, 2015. RESULTS Sustained myeloid engraftment with full donor chimerism was achieved in both groups (100%) at a median of 16 (10 - 26) days. Twenty-six patients (86.7%) in haplo-PBSCT group and all patients in MSD-PBSCT group achieved platelet recovery. There was no difference of the cumulative incidence of acute GVHD grade 2-4 (Fig. 1), chronic GVHD (20% vs 33.3%, P=0.581), transplantation-related mortality (TRM) (16.7% vs 0%, P = 0.121), relapse (33.3% vs 38.5%, P = 0.578, Fig 2) between haplo-PBSCT and MSD-PBSCT group. Donor age of 41yr and older was an independent risk factor for inferior leukemia-free-survival (27.8% vs 37.2%, P = 0.004). CONCLUSION In this cohort study, haplo-PBSCT showed similar outcomes in patients with refractory/relapsed AML compared with MSD-PBSCT. It suggested the feasibility of G-CSF-primed PBSC as a graft source in unmanipulated haplo-HCT under myeloablative conditioning, which was effective and tolerable for treatment of poor risk leukemia. Table 1. Characteristics of patients and donors Haploidentical donor Matched sibling donor P value Cases % Cases % Gender, n (%) Receipt Male 22 73.3 8 61.5 0.485 Donor Male 22 73.3 7 53.8 0.292 Age,y, median(range) Patient ≤40 y, n (%) 21 70 6 46.2 0.178 Donor ≤41 y, n (%) 13 43.3 5 38.5 1.000 AML, n (%) 1.000 CR2 5 16.7 2 15.4 NR/beyond CR2 25 83.3 11 84.6 Time to transp 0.51 ≥7m 14 46.7 8 61.5 Conditioning Regimen, n (%) 0.675 BuCy 22 73.2 9 69.2 TBIcy 4 13.3 1 7.7 FB 4 13.3 3 23.1 CD34+ in graft (106/kg) 0.499 ≥4.77 17 56.7 5 41.7 Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

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