One year follow up of 71 leukemic patients who received fludarabine and busulfan (FluBup) as myeloablative conditioning regimen for allogeneic PBSCT

M. Iravani, M. Tavakoli, A.R. Shamshiri, A. Mousavi, B. Bahar, A. Ghavamzadeh
2005 Biology of Blood and Marrow Transplantation  
We studied the effectiveness of a fludarabine/cyclophosphamidebased conditioning regimen without anti-thymocyte globulin in 23 aplastic anemia patients, who had no response to previous conventional pharmacologic treatment. Patients received oral busulphan 4 mg/kg/day/2 days, IV cyclophosphamide 350 mg/m 2 /day/3 days and fludarabine 30 mg/m 2 /day/3 days. For GVHD prophylaxis patients received MTX 5 mg/m 2 days ϩ1, 3, 6, and 11 and oral cyclosporin-A (CyA) 5 mg/kg/day, starting on day Ϫ1.
more » ... ng on day Ϫ1. Peripheral blood stem cell products were used with a median dose of 5.5 ϫ 10 6 CD34 ϩ /kg. The patients were followed for an average of 25 months. By a median of day ϩ11 an ANC Ͼ0.5 ϫ 10 9 /L was reached; and by day, ϩ12 the platelet count had reached Ͼ20,000 ϫ 10 9 /L. Acute grade I-II GVHD occurred in 4 patients, whereas limited chronic GVHD presented in 6 cases. Twenty one patients (91.3%) achieved engraftment. Two patients failed to engraft and 4 developed late rejection, two of these individuals died, 2 survive with high transfusion requirements, whereas 2 received a second peripheral blood stem cell infusion and achieved sustained engraftment. Currently 21 (91%) of the 23 patients are alive, whereas 19 of 21 (90%) remain in complete remission. The average cost was about fifteen thousand US dollars for this kind of non-myeloablative transplant. Non-myeloablative stem cell transplantation represents an affordable alternative to traditional more cytotoxic conditioning for severe aplastic anemia (SAA) patients. Long-term effects however, remain to be evaluated. Iravani, M.; Tavakoli, M.; Shamshiri, A.R.; Mousavi, A.; Bahar, B.; Ghavamzadeh, A. We are evaluating fludarabine (40 mg/m 2 on days Ϫ6 to Ϫ2) and busulfan (4 mg/kg/day on days Ϫ5 to Ϫ2) as a new conditioning regimen for allogeneic peripheral blood stem cell transplantation in leukemic patients with matched related donors. Seventy one patients were enrolled, 18 with high and 53 with standard risk (18 ALL, 35 AML, 16 CML and 2 MDS; Fϭ29 Mϭ42). The median patient age was 23.7 years (range, 2.4 -46.7). Cyclosporine was used as a prophylactic agent for GVHD (3 mg/kg IV till ϩ4, 10 mg/kg oral from day ϩ5). The median follow-up was one year (range, 50 -592 days). 91.5% and 15.5% developed mucositis and hepatic toxicity respectively which resolved with conservative therapy. There was no cardiac toxicity (except one patient with mild pericardial effusion and another with tachycardia). The median of highest serum creatinine level during hospitalization were 1.6 mg/dl (range, 0.8 -3.7; 24.3% with Cr Ͼ2) and serum cyclosporine level, at the same time, was 246 ng/ml (range, 9 -814). 7% experienced hemorrhagic cystitis (infection was ruled out) and 36.6% experienced moderate to severe headache. 38% and 14.1% of the patients showed grade 1, 2 and grade 3 acute GVHD respectively. Grade 4 acute GVHD was found in one patient. 50% and 7% showed limited and extensive chronic GVHD. 27% of patients became CMV ϩ (min ϩ17, max ϩ69). The median times for neutrophil and platelet recovery were 10 (min 0, max ϩ26) and 12 (min 0, max ϩ30) days. In day ϩ38, 86.7% of the patients had 90% or more, mononuclear chimerism (with STR-PCR technique; median, 97%; range, 25-100). 5 ALL and 8 AML patients relapsed (18.3% of all patients, post transplantation lymphoproliferative disease was found in one of them) and 8 (11%) died after relapse. Nonrelapse mortality was 15.5% (11 patients; acute GVHD grade IVϭ1, CMV infection and GVHDϭ2, CMV infectionϭ2, pneu-moniaϭ2, infectionϭ2, chronic GVHDϭ2). With a median follow up of one year (range, 1.6 -20 months), the probability of overall survival and disease free survival was 73% and 66% respectively. It could be beneficial to use fludarabine versus cyclophosphamide in standard conditioning regimen for leukemic patients because of reduced toxicity, low incidence of acute GVHD and facilitated donor engraftment. Hashmi, K.U.; Raza, S.; Khattak, B.K.; Ahmed, P.; Hussain, I. Armed Forces Bone Marrow Transplant Center, Rawalpindi, Punjab, Pakistan. ONE YEAR FOLLOW UP OF 71 LEUKEMIC PATIENTS WHO RECEIVED FLUDARABINE AND BUSULFAN (FLUBUP) AS MYELOABLATIVE CONDI-TIONING REGIMEN FOR ALLOGENEIC PBSCT ALLOGENEIC BONE MARROW TRANSPLANTATION IN ␤-THALAS- SAEMIA-SINGLE CENTER STUDY
doi:10.1016/j.bbmt.2004.12.060 fatcat:hykhghx3xzatzlcsijguobibcq