Patients with bone marrow failure syndrome (BMFS) are suffered from cytopenia and resulting requirement of transfusion. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the standard therapy for severe aplastic anemia (AA) with suitable sibling donor. However, it is true in many cases that alloHSCT can not be performed even in very severe AA due to no suitable donor. Although there were several reports of Alemtuzumab (ALM) for immune cytopenia and pure red cell aplasia, no report were published regarding ALM for BMFS. We studied the feasibility of ALM and cyclosporine A (CsA) for patients with BMFS. Inclusion criteria were transfusion-dependent BMFS including AA, myelodysplastic syndrome (MDS), pure red cell aplasia (PRCA). Prior IST or other drugs for BMFS except for ALM were not excluded. The dose of ALM was escalated from stage I dose (10mg on day 1, 20mg on day 2, and 30mg on day 3) to stage II dose (30mg/day for 3 days) along with CsA for at least 6 months. Prophylactic ciprofloxacin, acyclovir, and bactrim were given for first 2 months. Without partial response (PR) or more within 6 months, subsequent alloHSCT or antithymoglobulin therapy was allowed. Total 17 patients were enrolled. The majority was female (n=13, 76.5%). Median age was 48 (16–74) years. Diseases were 12 severe AA, 3 moderate AA and 1 hypoplastic MDS and 1 PRCA. All patients were transfusion-dependent. Fourteen patients were red cell transfusion-dependent and 12 patients were platelet transfusion-dependent. Median amount of transfused red cell, platelet concentrate and platelet apheresis prior to ALM-CsA were 6 (0–41), 3 (0–172) and 1 (0–22) units, respectively. Prior therapy were none in 13 (76.5%), anti-thymoglobulin in 3 (17.6%), and danazol in 1 (5.9%). Mean WBC, absolute neutrophil, hemoglobin and platelet were 3194 (600–6730)/mm3, 1365 (312–4257)/mm3, 7.3 (3.4–13.5)g/dl and 58K (3–334)K/mm3, respectively. Mean bone marrow cellularity was 11.9 (3–40)%. Patients received stage I dose in 13 and stage II dose in 4. Three patients could not receive full scheduled CsA because 2 patients died of infection and 1 patient underwent alloHSCT within 6 months after CsA. Median follow-up for response was 289 (91–691) days. Response to ALM-CsA were no response in 11 (64.7%), PR in 2 (11.8%), and CR in 4 (23.5%). Therefore, overall response rate was 6/17 (35.3%). Overall response in stage I dose and stage II dose were 5/13 (38.5%) and 1/4 (25%), respectively. All responsive patients showed their responses within 3 months. Median time to response was 55 (29–71) days. All CRs were converted from initial PR. Median time to CR and median time from PR to CR were 345.5 (91–691) and 278 (31–508) days. Neither diagnosis, fever nor skin rash during treatment did not affect the possibility of response to ALM-CsA (p=0.301, p=0.482, p=0.793, respectively). Toxicity during ALM was fever in 4 (23.5%), skin rash in 5 (29.4%), G1 ALT elevation in 7, G2 ALT elevation 2, G1 AST elevation in 5, and hyperbilirubinemia in 4 (G1 in 3, G3 in 1). There were no anaphylaxis, serum sickness or CMV reactivation. Three patients died of infection (n=2) or after alloHSCT (n=1). Four patients underwent alloHSCT after ALM-CsA treatment and 3 patients were successful.In spite of small number, ALM-CsA showed comparable response rate within 3 months after treatment. Therefore in conclusion, ALM-CsA is feasible and tolerable therapy for BMFS and stage I dose may be more recommendable.
Disclosure: No relevant conflicts of interest to declare.