Short Term Outcome after Allogeneic Stem Cell Transplantation in 70 Cases of Severe Aplastic Anaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5046-5046
Author(s):  
Parvez Ahmed ◽  
Khalil Ullah ◽  
Tariq M. Satti ◽  
Shahid Raza ◽  
Qamar-Un-Nisa Chaudhry ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anaemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Severe Aplastic Anaemia ◽  
Post Transplant ◽  
Matched Sibling

Abstract Allogeneic stem cell transplantation (SCT) from HLA matched sibling donor is the standard treatment option in younger patients with severe aplastic anaemia (SAA). In the current study outcome of 70 patients with SAA undergoing allogeneic SCT at our institution from July 2001 to June 2007 is presented. Median follow up time was 727 days (range 100–2187). Three patients received 2nd SCT due to graft failure or rejection so actual number of SCT in the patients was 73. Median age of the patients was 16 years (range 5–38), 55 males, and 15 females. Seventeen had major ABO mismatch while sex mismatch in the form of female donor to male patient was present in 23 cases, 7 had both major ABO and sex mismatch. Sixty four patients were CMV positive while 6 had CMV negative status. Conditioning regimens included; cyclophosphamide (Cy) 200 mg/kg with either antilymphocyte globulin (ALG) 45 mg/kg (n=33) or antithymocyte globulin (rabbit ATG) 11.25 mg/kg (n=26); Cy plus Campath 100 mg (n=6), fludarabine 150 mg/m2 plus Cy 300 mg/m2 and ATG (n=8). All patient undergoing 2nd transplant received conditioning with Cy, fludarabine and ATG. GVHD prophylaxis was given with cyclosporin (CSA) plus prednisolone (41) with or without short course of methotrexate (29). Patients received PBSC (10) or bone marrow (12) alone or both (48). Mean mononuclear and CD34+ cell doses were 5.59 x 108/Kg and 4.8 x 106/Kg respectively. Median time to neutrophil recovery was 11 days (range 7–24). Neutropenic fever was seen in 60% cases, with mean duration of fever being 8 days. In majority (66%) no focus of infection could be found. Various isolates included gram negative rods (n=6), staphylococcus (n=2) and fungi (n=5). Other post-transplant infections were tuberculosis (n=2), herpes zoster (n=2) and transfusion associated falciparum malaria (n=2). Post-BMT non-infectious complications included acute GVHD (24%), chronic GVHD (08%), hemorrhagic cystitis (14%), seizures (5%), and VOD (3%). Graft rejection and primary graft failure was seen in 3 and 2 cases respectively. Three of them received 2nd transplant and had successful recovery while the other 2 died of septicemia. Six patients died during peri-transplant period, 3 at day 100, and 8 beyond day 100. One patient died of unrelated cause at 2 years post-transplant. Main causes of death were septicemia (n=4), conditioning regimen toxicity (n=3), VOD (n=2), GVHD (n=2) and disseminated aspergillosis (n=2). The overall and disease free survival was 76%. In univariate analysis using Logrank and Wilcoxon test factors correlated with better survival were patient’s age <15 years, disease duration <6 months, previous transfusions <20 events, conditioning with fludarabine/Cy/ATG, and absence of chronic GVHD. SCT from HLA matched sibling donor is effective treatment modality in majority of the young patients with SAA.

A single Centre Experience with allogeneic Stem Cell Transplantation for Severe Aplastic Anaemia in Childhood

1997 ◽  
Vol 209 (04) ◽  
pp. 201-208 ◽  
Author(s):  
Ruth Ladenstein ◽  
Christina Peters ◽  
Milen Minkov ◽  
Waltraud Emminger-Schmidmeier ◽  
Georg Mann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anaemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Severe Aplastic Anaemia ◽  
Single Centre ◽  
Single Centre Experience

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.

scholarly journals Adding Azathioprine and Hydroxyurea Preconditioning to Alemtuzumab/TBI May Improve Donor Chimerism in Matched Sibling Donor Allogeneic Stem Cell Transplantation in Adult Sickle Cell Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 997-997
Author(s):  
Erfan Nur ◽  
Sacha S Zeerleder ◽  
Aafke E. Gaartman ◽  
Caroline E Rutten ◽  
Charlotte F.J. Van Tuijn ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Organ Damage ◽  
Sibling Donor ◽  
Donor Chimerism ◽  
Matched Sibling

Introduction Sickle cell disease (SCD) is a severe, inherited hemoglobinopathy, characterized by hemolysis, vaso-occlusive crisis (VOC) and progressive organ damage, resulting in poor quality of life and reduced life expectancy. Improvements in supportive care, use of (exchange) blood transfusions and hydroxyurea have resulted in better survival in SCD children. Nevertheless, SCD related organ damage continues during adult life, resulting in increased morbidity and mortality. Allogeneic stem cell transplantation is currently the only curative treatment option for SCD. In adults, myeloablative conditioning is associated with significant toxicity, primarily due to cumulative organ damage. Matched sibling donor (MSD) transplantation with non-myeloablative conditioning (alemtuzumab + 3 Gy total body irradiation (TBI)) using peripheral blood stem cells has shown promising results in adult SCD patients. In patients treated with this regimen the SCD phenotype resolved with only mild transplantation-related complications, but no reports of graft-versus-host disease (GvHD). However, a large part of these patients did not reach complete donor chimerism and graft failure rates of 8-13% have been reported with this regimen (Hsieh et al. JAMA, 2014; Saraf et al. Biol Blood Marrow Transplant, 2016). Adding azathioprine and hydroxyurea as preconditioning to the alemtuzumab/TBI regimen might improve donor chimerism and reduce risk of graft failure. In this study we prospectively investigate the effects of azathioprine/hydroxyurea preconditioning prior to alemtuzumab/TBI conditioning on donor chimerism and graft failure in patients receiving MSD allogeneic stem cell transplantation for SCD. Methods Adult SCD patients with complications refractory to standard care who had an HLA-identical sibling donor were eligible for this treatment. After 3 months of azathioprine 150mg qd and hydroxyurea 25mg/kg qd, erythrocyte exchange transfusion was performed on day -10, aiming for HbS <30%. Conditioning with alemtuzumab and TBI was started on day -7, as described by Hsieh et al (N Engl J Med, 2009). GvHD prophylaxis consisted of sirolimus. Data regarding SCD phenotype, donor chimerism and transplantation-related complications were collected prospectively. Results Eight patients (6 HbSS, 2 HbS-β+-thalassemia; median age 29 (range 21 - 49) years; 3 males) have been transplanted as of March 2018. All but one patient reached 100 % donor myeloid chimerism at 1 month. Myeloid chimerism remained stable in those who had reached full donor chimerism at one month (Figure 1A). One patient had 69% donor myeloid chimerism at 1 month, which increased gradually to 90 % at 9 months. Median T-cell donor chimerism at 3 months was 37% (range: 23 - 79%; n=6), increasing further during follow-up (Figure 1B). The percentages of donor myeloid and T-cell chimerism are higher than previously reported with alemtuzumab/TBI only (Hsieh et al. JAMA, 2014). All patients had a corrected SCD phenotype with mostly normalized hemoglobin levels at 3 months (from median 9,5 (IQR 7.8 - 10.7) g/dL at baseline to 12.4 (11.6 - 13.5) g/dL at 3 months, increasing further thereafter. Sirolimus tapering was started at 12 months in the first transplanted patient and stopped without affecting donor chimerism. There were no reports of SCD-related complications. One patient developed acute grade III intestinal GvHD, despite appropriate trough levels of sirolimus, though responded well to high dose steroids. Other treatment-related complications were mTOR inhibitor-associated stomatitis (n=5) responding well to local steroids, arthralgia that was moderately severe in 2 patients and progression of preexistent chronic kidney injury in one patient, which partially recovered after switching sirolimus to mycophenolate mofetil. Conclusion Azathioprine/hydroxyurea preconditioning prior to alemtuzumab/TBI conditioning is well tolerated and may result in improved (higher) donor chimerism after non-myeloablatieve MSD transplantation in SCD patients. Importantly, one patient developed acute GvHD. As (acute) GvHD following alemtuzumab/TBI conditioning has not been reported previously, a relation with the preconditioning (azathioprine) cannot be excluded. Longer term results of larger cohorts are needed to determine the place of azathioprine/hydroxyurea preconditioning in non-myeloablative MSD transplantation for SCD. Disclosures Nur: Novartis Pharmaceuticals: Consultancy. Zeerleder:Jazz Pharma: Speakers Bureau; Sanofi/Genzyme: Speakers Bureau; Alexion: Speakers Bureau.

Nonmyeloablative Allogeneic Stem Cell Transplantation: Hacettepe University Institute of Oncology Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5155-5155
Author(s):  
Yener Koc ◽  
Evren Ozdemir ◽  
Basak Oyan ◽  
Emin Kansu
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Post Transplant ◽  
Peripheral Stem Cells ◽  
Causes Of Deaths

Abstract The purpose of this study was to determine the feasibility and efficacy of nonmyeloablative allogeneic stem cell transplantation in patients with hematologic malignancies and metastatic renal cell carcinoma (RCC). Thirty patients with various pathologies (AML/MDS, n=9; CML, n=5; lymphoid malignancy, n=6; Multiple Myeloma, n=7; RCC, n=3) received a fludarabine (F)-based nonmyeloablative regimen (F+Busulphan, n=5; F+TBI, n=18; F+Cyclophosphamide, n=3; others, n=4), followed by unmanipulated peripheral stem cells from HLA-identical sibling donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and mycophenolate mofetil. Median age was 43 years (range, 17–62), median time from diagnosis to transplant was 1.6 years (range, 0.4–9.1). Patients underwent a median of 2 prior chemotherapy regimens (range, 0–7). Prior stem cell transplantation failed in seven patients (23%) (autologous, n=6; ablative allogeneic, n=1). Disease phase prior to transplant was complete or partial remission in 16 patients (CR, n=12; PR, n=4) and active disease in 14 patients (Primary refractory, n=1; Relapse, n=10; Untreated, n=3). Recipients were male and donors were female in 15 transplants (50%). The median numbers of mononuclear and CD34+ cells infused were 8.8 x 108/kg (range, 4–26 x 108/kg) and 9.7 x 106/kg (5.2–32.5 x 106/kg) respectively. Neutrophil engraftment achieved after a median of 9 days (range, 6–12) and platelet engraftment occurred after a median of 11 days (range, 9–19). In twelve (40%) patients, absolute netrophil count did not fall below 500/mm3 and 14 patients (47%) required no platelet transfusions. The patients received a median of 2 donor lymphocyte infusions (range, 0–8). Nine patients (30%) had acute GVHD (Grade II-IV, n=5, 17%) and 12 patients (40%) had chronic GVHD (limited, n=4; extensive, n=8, 27%). Three patients (10%) died of nonrelapse treatment-related complications within 100 days post-transplant (Pneumonia, n=2; Bronchoalveolar hemorrhage, n=1). Two patients had graft failure at day 100 post-transplant. Twenty two patients (73.4%) are currently alive with a median follow-up of 6 months. Primary causes of deaths (n=8, 26.6%) are as follows; GVHD (n=3), pneumonia (n=2), bronchoalveolar hemorrhage (n=1), and relapse (n=2). Among 22 evaluable patients, response was obtained in 18 patients (82%) (CR, n=14; PR, n=2; stable disease, n=2) and 4 patients relapsed. Our data suggest that nonmyeloablative allogeneic transplantation is a safe and effective treatment strategy in hematological malignancies.

Allogeneic Hematopoietic Stem Cell Transplantation for Children with Myelodysplastic Syndrome: A Report of a Korean Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4500-4500
Author(s):  
Jeong A. Park ◽  
Ho Joon Im ◽  
Jong Jin Seo
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Refractory Anemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Matched Sibling

Abstract Abstract 4500 Purpose: Accounting for 4% of childhood hematological malignancy, myelodysplastic syndrome (MDS) is very rare in children than in adults. Therapy of these disorders has been associated with intensive treatment related toxicities and a high risk of relapse. Children with refractory anemia (RA)/refractory anemia with excess blast (RAEB) usually do not respond to acute myeloid leukemia (AML)- type chemotherapy, and chemotherapy without hematopoietic stem cell transplantation (HSCT) resulted in survival rates below 30%. Since failure rates after HSCT are lower in this group when treated at diagnosis, HSCT should be strongly considered, especially when a fully matched sibling donor (MSD) is available. The optimal treatment for children with RA/RAEB without matched sibling donor is presently undetermined. Some of them have stable disease course and require no therapy for years. However, aggressive treatment with HSCT using alternative donors should be considered for severe cytopenia. We analyzed the results of allogeneic HSCT in 16 children who were diagnosed with de novo MDS in a single Korean center. It is the first report about the outcome of HSCT for Pediatric MDS in Korea. Patients and Methods: Between November 1997 and June 2011, 16 children with MDS underwent allogeneic HSCT at Asan Medical Center. These patients had RA (n=7), and RAEB (n=9). Peripheral blood smears, bone marrow aspirates and biopsies of all patients were assessed by central morphology review according to the WHO classification. HSCT was recommended if the patients developed neutropenia (ANC<500/μ L) or transfusion dependency. Median age at transplant of 9 males and 7 females was 8.9 years (range 1.6–20.3). Cytogenetic analysis at diagnosis was available in 15 patients. Nine of them had a normal karyotype and 6 patients had miscellaneous chromosomal changes, but nobody had monosomy 7. Six patients (33%) were grafted from an MSD, whereas the remaining were transplanted from an unrelated donor (UD) (n=6), umbilical cord blood (n=3) or a haplo-identical family donor (n=1). All patients received myeloablative conditioning including busulfan (n=13) or total body irradiation (n=3). The median number of transfused CD34 cells was 8.2×106/kg for bone marrow or peripheral blood stem cell transplantation, and 1.3×105/kg for umbilical cord blood transplantation (UCBT). Graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate was used for 14 patients, and cyclosporine and MMF were used for UCBT. Results: Sustained neutrophil engraftment was achieved in 11 patients, and five patients experienced graft failure. One patient died of subarachnoid hemorrhage on day 1 before engraftment, and 4 patients experienced primary graft failure; all patients were regrafted from haplo-identical related donors. Three patients are alive without disease, but one patient died 103 days after third HSCT from CMV pneumonia. The cumulative incidence of grade II-IV acute GVHD in the 15 evaluable patients was 0.27, and they were all manageable. Two patients developed extensive chronic GVHD; one patient died from disease progression to AML 579 days after HSCT, the other died from fungal pneumonia and intracranial hemorrhage 113 days after HSCT. With a median follow-up of 6.0 years (range 0.1–14), the cumulative incidence of treatment related mortality (TRM) and relapse was 0.19 and 0.20, respectively. The Kaplan-Meier estimates of overall survival (OS) and event free survival (EFS) at 5 years were 0.64 and 0.41. The diagnosis of RAEB was positively associated with relapse (P=0.02) and significantly decreased OS (P=0.024). Donor type was not significantly associated with TRM, graft failure, relapse and outcome. While acute GVHD did not affect the outcome, chronic GVHD significantly affected OS (P=0.0013). Conclusions: Though our results showed considerable early engraftment failure rates (31.3%), most of all were successfully regrafted form haplo-identical related donors, and showed comparable treatment outcome. Allogeneic HSCT following a myeloablative conditioning can offer a high probability of cure for children with MDS, however, efforts to further reduce the rejection, relapse and TRM in patients undergoing allogeneic HSCT are needed. Disclosures: No relevant conflicts of interest to declare.

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