Pulse Cyclophosphamide Therapy in Refractory Warm Autoimmune Hemolytic Anemia: A New Perspective

Abstract

Treatment of steroid refractory autoimmune hemolytic anemia (AIHA) is challenging especially with no evidence based consensus guide lines and limited resources. The aim of this study was to evaluate the efficacy of pulse cyclophosphamide therapy in patients with severe refractory warm AIHA. The prospective study was designed to evaluate the efficacy of pulse cyclophosphamide-1 g/month for four consecutive months-in 17 patients (10 males and 7 females) with severe refractory warm AIHA [13 primary AIHA and 4 (females) secondary to SLE], all studied patients failed to respond to high dose of steroid therapy ± azathioprine ± intravenous immunoglobulin ± oral cyclophosphamide. Mean hemoglobin level, reticulocytic count and direct antiglobulin test were assessed before and after cyclophosphamide treatment every month. After the 4th cycle of cyclophosphamide (82 %, 14 patients) achieved partial response while the remaining (17 %, 3 patients) showed no response, while after 6 months follow up 47 % (8 patients) show complete response, while 53 % (9 patients) showed partial response. The mean hemoglobin levels were significantly increased after the 1st, 2nd, 3rd and 4th months of pulse cyclophosphamide therapy when compared to before treatment (P < 0.01, P < 0.001, P < 0.001 and P < 0.001) respectively, and the mean reticulocyte (%) were significantly decreased after the 2nd, 3rd and 4th months (P < 0.05, P < 0.01 and P < 0.001) respectively. We conclude that pulse cyclophosphamide therapy is well tolerated and induces good response in patients with severe refractory warm AIHA.

Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting

“…In another study, 4/7 patients responded but no patient achieved a steroid-independent sustained response [82]. Two studies reported success with intravenous cyclophosphamide [110,111].…”

“…All patients responding to either 50 mg/kg (ideal body weight)/day for 4 days (4 had primary warm AIHA) without autologous stem cell transplantation or 1 g monthly for 4 months (13 had primary warm AIHA). Important side effects include myelosuppression, infections, urotoxicity, secondary malignancy, and infertility [111].…”

The diagnosis and management of primary autoimmune haemolytic anaemia

“…50–100 mg daily) with or without prednisolone, there are few data on dosing or efficacy and, given its mutagenic potential, oral cyclophosphamide cannot be recommended over second line steroid‐sparing agents. Higher intravenous doses also appear effective, for example 50 mg/kg/day for 4 days (Moyo et al , ) or 1 g monthly for 4 months (Thabet & Faisal, ).…”

How I treat autoimmune hemolytic anemia

“…The more commonly used treatments along with their corresponding dosing schedules are displayed in Table 1. [36][37][38][39][40][41][42] Patterns of care studies are not available, but single-agent rituximab is perhaps the most commonly used treatment in this setting and is our first choice after splenectomy relapse. In a meta-analysis of 21 studies that investigated rituximab, the overall response (OR) and CR rates were 79% and 42%, respectively.…”