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/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 +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 · 10 6 CD34 + /kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 · 10 9 /L was reached; and by day +12, the platelet count had reached >20,000 · 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; 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 reducedintensity 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.

Low incidence and severity of graft-versus-host disease after outpatient allogeneic peripheral blood stem cell transplantation employing a reduced-intensity conditioning

“…In our study, despite the use of peripheral blood as the source of stem cells in patients with SAA, only 15.4% of 26 patients developed acute grades II–IV GVHD and 19% cGVHD, which was limited in all cases. These results are similar to those reported in a previous multicenter study in Mexico (39). Interestingly, in India, the use of a fludarabine‐based protocol and PBSCs in patients with SAA resulted in respective rates of aGVHD and cGVHD of 21% and 31%, with an OS of 85% (40).…”

“…Previous reports on the use of PBSCs in the treatment of SAA have shown an increased incidence of cGVHD, in some cases with a high mortality (38). In contrast, it has been suggested that the use of non‐myeloablative conditioning regimens using fludarabine without high doses of cyclophosphamide is not associated with an increase in GVHD (39, 40), with acute and cGVHD presenting in 5–30% and 25–60% of patients, respectively. In our study, despite the use of peripheral blood as the source of stem cells in patients with SAA, only 15.4% of 26 patients developed acute grades II–IV GVHD and 19% cGVHD, which was limited in all cases.…”

The use of a fludarabine‐based conditioning regimen in patients with severe aplastic anemia – a retrospective analysis from three Indian centers

“…The major cause of early mortality was sepsis, and this mortality is related to the fact that approximately 28% of patients had sustained fever or fungal infection at the time of HSCT. Our previous experience has shown us that waiting for resolution of infection meant that a majority may not ultimately make it to transplant, and it is possible to successfully transplant patients with aplastic anemia who have active fungal infection at the time of HSCT . The use of this conditioning regimen is associated with a good five‐yr overall survival of 75.8%.…”

“…To reduce the risk of graft failure and improve outcome, modification of conditioning regimens using a fludarabine‐based conditioning has been attempted in a number of small studies . We have reported previously along with other groups the utility of using fludarabine‐based regimens in both heavily transfused patients as well as in patients with active infection at the time of HSCT . Fludarabine‐based regimens have also been used in patients undergoing unrelated stem cell transplants for SAA and as conditioning in older patients with SAA .…”

Fludarabine‐based reduced intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia and fungal infections

“…In developing countries, patients generally have to pay for their transplants without any financial help from either the government or the insurance sector, and transplant physicians must choose the best time to take up a patient for HSCT, to avoid wasting too much of their scarce Cell dose (·10 8 MNC/kg) 5.8 (1.9-8.5) ANC >500/mm 3 11 d (9-14) ANC >1000/mm 3 12 d (10-15) Platelet count >20 000/mm 3 resources. Fludarabine-based protocols provide an attractive option for HSCT in patients with AA, as the minimal toxicity and rapid engraftment associated with these protocols make them ideal for use in patients with active infections (8,9,12). They are also associated with a considerable reduction in costs, making them suitable for use in developing countries (13,14).…”