Allografting in patients with severe, refractory aplastic anemia using peripheral blood stem cells and a fludarabine-based conditioning regimen: The Mexican experience

Abstract

We studied the effectiveness of a fludarabine/cyclophosphamide‐based 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/m2/day/3 days, and fludarabine 30 mg/m2/day/3 days. For GVHD prophylaxis, patients received MTX 5 mg/m2 days +1, +3, +6, and +11 and oral cyclosporin A (CyA) 5 mg/kg/day, starting on day −1. Peripheral blood stem cell products were used with a median dose of 5.5 × 106 CD34+/kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 × 109/L was reached; and by day +12, the platelet count had reached >20,000 × 109/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; 2 of these individuals died, 2 have survived 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 USD 15,000 for this kind of reduced‐intensity allotransplant. Reduced‐intensity 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. Am. J. Hematol. 81:157–161, 2006. © 2006 Wiley‐Liss, Inc.

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

“…These figures are considerably lower when compared with most previous reports on allogeneic transplantation for AA. [15][16][17][18][19] Because of the small number of patients with GVHD, it is not possible to conclude from our study whether a high stem cell dose increases its risk. For haematological disorders in general, investigators have found a greater risk of chronic GVHD with PBSC transplant in the setting of a large CD34 þ cell dose.…”

“…Two studies have mentioned the median CD34 þ cell count but have not analysed its significance with respect to outcome, as this was not their primary study objective. 15,16 Some researchers have considered the total mononuclear cell count as a variable with potential influence on graft failure and OS. 5,6,[17][18][19] Other published studies to date have not included CD34 þ cell dose in their analysis.…”

Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen

“…17 These results reinforce encouraging survival estimates observed in previously reported studies without a comparative group, using such Flu-based regimens independently of patient age. [13][14][15][16] In older patients, the comparison of Flu-based to standard HSCT will certainly need to be further evaluated in a still larger number of patients to allow a definitive conclusion to be drawn.…”

“…8,9 Such Flu-based regimens have been explored in various nonmalignant diseases without conferring a significant survival advantage when compared to conventional myeloablative regimens. 10 In patients with SAA specifically, several previous case reports 11,12 or non-comparative studies [13][14][15][16] have reported encouraging results in the setting of HLA-matched related HSCT. The EBMT SAA working party has recently reported a favorable experience using Flu-based HSCT in SAA patients transplanted with unrelated (n=33) or family mismatched (n=5) donors.…”

Management of adult patients older than 40 years refractory to at least one immunosuppressive course: HLA-identical sibling HSCT using fludarabine-based conditioning

“…8 In patients with SAA specifically, several noncomparative studies have reported encouraging results in the setting of HLA-matched related HSCT. [9][10][11][12][13] A recent report from the EBMT SAA working party retrospectively analyzed 30 patients older than 30 years receiving reduced-intensity conditioning HSCT (using fludarabine 30 mg/m 2 Â 4, CY 300 mg/m 2 Â 4 and most with ATG, namely a FCA regimen) and compared their outcome with a control group receiving the standard regimen (CY þ / À ATG) over the same study period (1998-2007). 14 Recipients of fludarabine-based conditioning had a higher probability of ageadjusted overall survival than the control group (P ¼ 0.04).…”