Chemotherapy Plus Hematopoietic Growth Factor for Refractory Paroxysmal Nocturnal Hemoglobinuria: Diminishing PNH Clone and Stimulating Hematopoisis

Even complement inhibitor against C5 Eculizumab has been used in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) acting as a “dam” protecting PNH clone and storing higher risk of hemolysis. So we carried out a study to investigate the efficacy and safety of chemotherapy plus growth factors, a traditional treatment for malignant hematological diseases, aiming at diminishing PNH clone and stimulating hematopoisis, in patients with refractory and relapsed PNH.

10 patients were enrolled in this study. These patients were admitted into General Hospital affiliated to Tianjin Medical University(TMU) between 2006 to 2010, receiving either DAG (DNR 40mg/d, d_1–2; 20mg/d, d₃; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) or HAG (HHT 2–3mg/d, d1-5; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) regimen chemotherapy intravenously every 4 weeks for several cycles. The primary end points were the improvement of hemoglobin levels, decreased proportion of PNH clone and dosage of corticosteroid. Biochemical indicators of intravascular haemolysis and adverse events were also assessed.

All patients responded well. Overall improvement for anemia was achieved, transfusion independence(HB can keep more than 6g/L without transfusion) was achieved in 4 patients, hemoglobin levels reached normal gradually in 1 of them, 2 patients got prolonged transfusion interval, another 4 patients did not need transfusion all the time. Elevation of hemoglobin from (58.1±12.12) g/L to (90.20±21.55) g/L (P=0.000) was achieved for the 10 patients. The dosage of corticosteroid decreased significantly from (45.84±19.05)mg to (13.00±6.75)mg (P=0.000). The results of flow cytometry demonstrated that CD59⁻ and CD55⁻ erythrocytes and granulocytes in peripheral blood decreased significantly in 8 patients [(20.87±11.68)% vs (7.97±10.02)%, P=0.004 for CD59⁻ erythrocytes; (63.76±25.36)% vs (28.44±23.50)%, P=0.002 for CD55⁻ erythrocytes; (68.25±26.05)% vs (59.53±24.60)%, P=0.007 for CD59⁻ granulocytes; (81.47±26.13)% vs (68.14±26.53)%, P=0.003 for CD55⁻ granulocytes]. Indicators for haemolysis also improved. In 10 patients, apart from 1 patient with normal IBIL and TBIL all the time, IBIL decreased significantly from (36.8±29.2) U/L at baseline to (18.1±12.4) U/L (P= 0.015). Free hemoglobin level, Rous test, Ham ‘s test were carried out only in some of the patients and results of which were also encouraging. No patients died during chemotherapy; most common adverse events were infection, nausea, vomiting and fatigue. The duration of bone marrow depression ranged from 10 to 33 days.

DAG/HAG regimens Chemotherapy was an effective, safe and promising therapy for PNH.

No relevant conflicts of interest to declare.