Plerixafor, cyclophosphamide and G‐CSF and Blood cell mobilization in a patient with acute promyelocytic leukemia

To the Editor, Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia with distinct morphologic, cytogenetic and molecular features. Therapy of APL has progressed remarkably in the last 30 years with the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) and cures are now achieved in about 90% of patients with APL. High-dose chemotherapy and a transplant of autologous blood cells is widelyused to treat patients who relapse and achieve a 2nd remission. However, it is sometimes difficult to obtain sufficient numbers of blood cells for an autotransplant using chemotherapy and/or G-CSF. In patients with plasma cell myeloma or lympho-proliferative diseases, plerixafor, a molecule which blocks the interaction between CXCR4 and SDF-1, is added to the collection strategy. However, plerixafor is rarely used in the setting of autotransplants for myeloid leukemias because it may also mobilize leukemia cells resulting in leukemia contamination of the autograft. We describe blood cell mobilization with cyclophosphamide, G-CSF and plerixafor in a patient with APL in 2nd complete remission who failed a prior mobilization attempt with G-CSF alone. A 37-year-old woman developed high-risk APL according to PETHEMA risk stratification (WBC 20 3 10E1 9/L and platelets 9 3 10E1 9/L) in July, 2011. She received induction treatment with idarubicin and ATRA achieving a complete hematologic, cytogenetic and molecular remission. She then received 3 courses of consolidation chemotherapy with ATRA, an anthracycline and cytarabine followed by maintenance chemotherapy with 6-mercaptopurine, methotrexate and ATRA over 2 years. But relapsed in June 2014. She achieved a 2nd hematologic, cytogenetic and molecular remission following re-induction therapy with ATO (0.16 mg/kg/d) and ATRA (45 mg/mE1 2) followed by one cycle of consolidation chemotherapy with the same regimen. She was referred to our center for high-dose chemotherapy and an autotransplant. In February 2015, we tried to collect blood cells after giving G-CSF, 10 mg/kg/d for 5 days subcutaneously. An apheresis was not done because the CD34-positive cell concentration in her blood was only 9.4/ml on day 14. In March, 2015 a 2nd mobilization was done with cyclophosphamide 1.5 g/mE1 2 followed by G-CSF, 10 mg/kg/d, the next day. On day 18 the CD34-positive cell concentration was 2.2/ ml (WBC 22,000 3 10E1 9/L). Plerixafor (Revixil Gador Laboratories), 240 mg/kg, was given subcutaneously 11 h before beginning the apheresis. The blood CD34-positive cell concentration increased to 25/ml. We collected 2.41 3 10E1 6 CD34-positive cells/kg on a Spectra Optia (TerumoBCT, Lakewood, CO) processing a blood volume of 22.1 L (198 ml/kg) in one apheresis. The collected cells were frozen and a sample tested for PML/RARa transcripts by nested PCR. No transcripts were detected. Pretransplant conditioning was with intravenous busulfan 3.2 mg/kg/d and fludarabine 40 mg/ mE1 2/d on days 26 to 23 followed by the infusion of the defrosted blood cells. G-CSF, 10 mg/kg/d, was given day 15 until granulocytes were >500 3 10E1 3/L for 2 consecutive days. Granulocytes and platelets recovered on days 116 and 122 and she continues in hematological, cytogenetic and molecular remission 1 year later. Plerixafor facilitates collection of blood cells in patients with plasma cell myeloma and lymphoma who are poor mobilizers. Risk factors for poor mobilization include age 60 years, extensive prior chemotherapy, low platelets, and prior use of alkylating drugs and radiotherapy. As discussed, plerixafor is rarelyused to mobilize blood cells in patients with leukemia because of concern of also mobilizing leukemia cells with resultant contamination of the autograft. Our data and others suggest plerixafor can mobilize blood cells in a patient with APL in 2nd remission without contaminating the graft with leukemia cells. A similar approach is reported in Ph1-positive lymphoblastic leukemia (ALL).