Comparative Effects of Transfusion Program, Hydroxyurea or Stem Cell Transplant on Frequency of Hospitalisations in Pediatric Sickle Cell Patients.

Frequent vaso-occlusive crisis (VOC) and acute chest syndromes (ACS) cause high morbidity and early death and justify intensification of treatment. We report the comparative effects of Hydroxyurea (HU), Transfusion program (TP) or Stem Cell Transplant (SCT) on VOC and/or ACS occurrence in 76 SS/Sb0 patients.

Patients and Methods: This study only concerned the patients always followed and hospitalized in our pediatric center in Creteil, from 1979 to June 2004: among this cohort of 256 SS/Sb0 patients, 76 received a treatment intensification justified by a high frequency of hospitalizations (³ 3 VOC/y or 2 ACS/y). For this indication, HU was proposed since 1992 in 53 patients older than 3 years of age without abnormal cerebral velocities on Trans-cranial Doppler (TCD), TP in 42 patients younger than 3 years of age or having abnormal TCD (> 200 cm/sec) or HU failure in VOC/ACS frequency reducing, and SCT was performed in 15 patients with an available HLA identical sibling donor (14/15 successful). Several patients successively received different treatments: HU-TP (n=19), HU-TP-SCT (n=5), TP-SCT (n=6) and one patient who rejected the graft was treated with HU. We compared (student t-test) the causes, the frequency and duration of hospitalizations occurred during the year preceding the treatment intensification with those observed after the intensification program. For transplanted patients, we distinguishly considered the events having occurred during the first year post-transplant and those having occurred after.

Results: Mean (± SD) follow-up before intensification was 8.1 years (± 4.5) with 2.3 hospitalizations/year (± 2.2) occured since birth. During the year preceding the treatment intensification, an higher number of hospitalizations (3.9 ± 2.1) occurred with 24.3 days of hosp (± 19.1) and the mean number of VOC was 2.3 (± 2) and ACS was 0.5 (± 0.8). After intensification, number of hospitalizations and VOC and ACS, duration of hosp significantly (p<0.001)decreased. On HU, with a mean follow-up of 4.7 years (± 3) in 53 patients, 1.7 (± 1.5) hosp/year, with 8.8 days/year (± 9.3), 1 VOC/year (± 1) and 0.2 ACS/year (± 0.4) occurred. On TP, with a mean follow-up of 2.6 years (± 2.5) in 35 patients, 1.2 hosp/year (± 1.2) with 5.5 days/y (± 6.2), 0.4 VOC/y (± 0.6) and 0.04 ACS/year (± 0.1) were observed. SCT was performed in 15 patients frequently experiencing VOC/ACS: during the first year post-transplant, the mean (± SD) number of hosp. was 3.1 (± 2.1) with 60.1 (± 26.1) days of hosp. related to the procedure and infectious complications. With a mean (± SD) follow-up of 4.1 years (± 3.8), after exlusion of the first year post-transplant, the number of hosp, days of hosp/year were respectively 0.3 (± 0.5) and 1.3 (2.1) and 0.01 (± 0.04) VOC or ACS/y. Number of hosp, days of hosp, VOC, ACS were highly significantly (p=0.001) lower after SCT than on HU therapy and the prevention of VOC (p<0.001) and ACS (p=0.04) was better on TP than with HU.

Conclusion: Intensive treatments were significantly efficient to decrease the number and the duration of hospitalizations and the number of VOC and ACS. TP maintening HbS level < 40% was significantly more efficient than HU to prevent VOC (p<0.001) and ACS (p=0.03). SCT, after the 1 year post-transplant was the most efficient (p<0.001) to reduce the number and duration of hospitalizations and VOC/ACS rate occurrence. However, benefits/risks and costs of each treatment have to be prospectively assessed.