Reduced-Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Patients Older Than 60 Years.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with hematological malignancies but its use is limited to young patients without comorbidities.

The aim of present study was to evaluate the efficacy of a reduced-intensity conditioning (RIC) consisting of fludarabine and TBI in older patients aged 60 to 70 years.

Methods: between March 2000 and May 2003, 22 patients (median age 62 years; range 59–70) with hematological malignancies (n=18 AML/MDS; n=1 ALL; n=1 CLL; n=1 myelofibrosis) and solid tumor (n=1 renal cell carcinoma) were treated with a RIC regimen based on fludarabine (30 mg/m² x 3–5 days) and 200 cCy TBI followed by alloHSCT from a matched-sibling donor. GVHD prophylaxis consisted of cyclosporine and mycophenolate. The source of stem cell was blood in all patients. The median CD34+ content of the grafts was 5.7 x 10⁶/kg (range 3.1–8.7). Three patients had received a prior allograft. Eleven patients had active disease at transplantation, 5 patients were untreated and 6 were allografted in complete remission (CR).

Results: neutrophil recovery occurred in 15 patients (68%) at a median time of 16 days (range 8–33). One patient who died early after transplantation (day +5) and 4 patients who experienced an autologous reconstitution, failed to reach this threshold; 2 patients did not become granulocytopenic. Fifty-eight percent of the patients had > 90% donor chimerism on day +30. Twelve of 17 evaluable patients (70%) developed acute GVHD (n=5 grade I; n=6 grade II; n=1 grade III), whereas chronic GVHD was observed in 11 of 13 patients (85%) surviving more than 100 days (limited in 7 cases and extensive in 4 cases). The probability of acute GVHD grades II–IV and extensive chronic GVHD was 43% and 31% respectively. Two patients died of treatment-related complications: 1 patient died of toxic encephalopathy on day 5 after transplantation and 1 patient of thrombotic thrombocytopenic purpura on day 915. The 100-day nonrelapse mortality for the whole population was 5%.Ten patients (45%) died as a result of relapse. With a median follow-up of 586 days (range 50–1128) 10 patients are alive (9 with CR and 1 with relapsed disease).The probability of overall survival at 2 years was 86% for patients treated in CR or at diagnosis and 9% for patients transplanted in advanced phase of disease (p= 0.0008).

Conclusion: Our analysis would suggest that for patients older than 60, this RIC regimen is well tolerated and associated with a low incidence of transplant-related mortality and serious acute and chronic GVHD. The leukemic burden at time of transplant has proven to be the most important risk factor for the outcome.