scholarly journals Comparison of Post-transplant Cyclophosphamide Containing Immunosuppressive Regimen with Standard Immunosuppressive Regimen in Allogeneic Stem Cell Transplantation from Matched Sibling Donor

2021 ◽  
Vol 9 (3) ◽  
pp. 269-275
Author(s):  
Osman KARA ◽  
Tayfun ELİBOL
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Immunosuppressive Regimen ◽  
Post Transplant ◽  
Sibling Donor ◽  
Matched Sibling

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.

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.

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