Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome.

PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12% and 38% +/- 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.

In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1.

Correction of post-renal transplant erythrocytosis by enalapril.

We studied whether post-renal transplant erythrocytosis (PRTE) could be corrected by enalapril with minimal side-effects, thus avoiding iterative phlebotomies or bilateral nephrectomy of native kidneys. From our renal transplant patients, 12 presented a true PRTE as defined by a 51-Cr red blood cell mass (RBCM) above 32 ml/kg for women and above 36 ml/kg for men. Secondary polycythemia was ruled out: all the patients had a normal renal artery pulsed ultrasonography; in all cases the blood arterial 02 saturation was above 96%. Bone marrow aspiration and histology were performed for each patient: none of them showed evidence of Vaquez disease. All of them had stable renal function i.e. the mean serum creatinine was 112.8 +/- 26.3 mumol/l. They all received the same immunosuppression: azathioprine; ciclosporine A; methylprednisolone. PRTE occurred within the first year post transplant (median 7.5 months; range: 2-34). Their mean RBCM was 37.38 +/- 2.7 ml/kg. Their mean serum value of Epo was 17.41 +/- 13.5 mU/ml (range: 9.1-54). After informed consent, all patients received enalapril starting with 5 mg/day, progressively increased to 20 mg/day, if necessary, in order to maintain the hematocrit below 45%. The mean daily dosage of enalapril was 13.75 +/- 6.1 mg (range: 5-20). The mean follow-up was 14.8 months (range: 3.5-29.5). There was no change in renal function (mean serum creatinine: 126.3 +/- 35 mumol/l). A successful response to enalapril was obtained with a median of 40 days (range: 20-120). 11 patients out of 12 responded to enalapril with a decrease of Hb (14 +/- 2 g/dl vs 16.8 +/- 1.04 g/dl; p = 0.0006) and Ht (41.9 +/- 6.17% vs 51.14 +/- 2%; p = 0.0002) without a significant decrease of Epo (8.1 +/- 3.87; p = 0.1). One patient did not respond to enalapril nor to captopril, but did respond to a combined treatment of enalapril and theophilline. Moreover, all PRTE patients but two did not have Epo levels, before enalapril, above the normal range, suggesting mechanisms other than Epo overproduction by native kidneys i.e. erythropoiesis dysregulation. In conclusion, all patients but one were successfully treated by enalapril without side effects. The treatment was effective as early as 3 weeks from the start and avoided the need for iterative phlebotomies and nephrectomy of native kidneys.