The treatment of steroid-refractory acute graft-versus-host disease (aGVHD) remains a clinical challenge, for which no standard therapy exists. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) that has been successfully used as part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) to prevent GVHD. The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (>or=grade II) following HSCT. Eighteen patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days. Response was assessed at day 28 following initiation of alemtuzumab. Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV. The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3. Fifteen patients (83%) responded to alemtuzumab, including 6 (33%) with complete response. All 3 unresponsive patients died of GVHD. Ten of 15 responders are alive at median follow-up of 11 months (range: 3-24). Infections occurred in 14 patients, including cytomegalovirus (CMV) reactivation in 11. Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively. Alemtuzumab was well tolerated, and induces promising response rates in steroid-refractory aGVHD.

Corticosteroids therapy is the mainstay of treatment for GVHD, however, it heavily impacts on post transplant morbidity and new modalities are continually needed. Alemtuzumab a humanized monoclonal antibody to CD52 has been used mainly as GVHD prophylaxis. Only a few patients have been treated with this antibody. From December 2004 to May 2006, we recruited 13 steroid refractory acute GvHD patients in a prospective trial evaluating the efficacy of alemtuzumab (Campath 1H) after exclusion of other severe HST-related complications. Primary endpoints were response to treatment after 14 and 28 days. Secondary endpoints were side effects and incidence of infectious complications. Treatment consisted of Campath 1H 10mg given s.c. on days 1–5. Median age was 33 years old (range:1–59) years, a fludarabine-based reduce intensive conditioning (RIC) regimen was used and the hematopoietic cells were obtained from HLA-identical siblings in 12 cases and one patient received stem cell from umbilical cord blood. All but one received CSA and MTX for GvHD prophylaxis. GvHD affected gut in 6 cases, skin in 3 liver in 4, and combination of gut and skin in 6 patients. In 6 of the 13 patients the clinical manifestations of GVHD were noticed after the first 100 days of HSCT. Complete resolution of GvHD, partial response and no response were seen respectively in 23%, 62% and 15%. Six over the 13 patients were able to decrease steroid use. Five patients developed CMV (pp65) reactivation and 3 of them were successfully treated with valganciclovir. All patients maintained complete chimerism during and after alemtuzumab therapy, and after a median follow-up of 4 months (range, 1– 17months), 8 remain alive, 3 without evidence of GVHD. Five patients died, 3 due to GvHD and the others due to infectious complications. This preliminary study suggests that alemtuzumab is a well-tolerated agent and has a beneficial effect in the treatment of refractory GvHD. It is only a pilot study and more studies are needed, but we suggest that this modality could be used early in the management of these patients in order to improve quality of life and reduce the long-term side effects of corticosteroids.

The incidence of GVHD was lower than in other series using conventional myeloablative preparative regimens. Most importantly, the severity of GVHD did not significantly affect the long-term survival.

A group of 21 consecutive patients aged 4-20 (median 13) years was prospectively allografted using a reduced intensity preparative regimen. The group included both malignant (acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia) and nonmalignant (aplastic anemia, Diamond-Blackfan anemia, thalassemia major and adrenoleukodystrophy) conditions. Follow-up times ranged between 16 and 1038 days. Four of 21 patients (9.5%) developed acute graft-versus-host disease, and 2 of them died, whereas limited chronic graft-versus-host disease was observed in 2 of 15 cases. The 100-day mortality was 19%. Median overall survival was above 1038 days, whereas the 34-month survival was 55%. These data show that reduced intensity stem cell transplantation in children permits rapid engraftment from siblings with little toxicity.