Plerixafor and autologous stem cell transplantation: impressive result in a chemoresistant testicular cancer patient treated with high-dose chemotherapy.

Plerixafor, a CXCR4 antagonist, induces the rapid release of hematopoietic progenitor stem cells from the bone marrow into peripheral blood; it is approved for autologous hematopoietic progenitor stem cell mobilization in multiple myeloma and non-Hodgkin's lymphoma patients. We report the case of a 34-year-old patient with metastatic testicular embryonal carcinoma who was extensively and in vain pretreated with chemotherapy and failed to mobilize an adequate number of hematopoietic progenitor stem cells following high-dose chemotherapy, with the support of granulocyte colony-stimulating factors. After a cycle of high-dose cyclophosphamide associated with granulocyte colony-stimulating factors, plerixafor was administered to the patient, with the clinical evidence of an increase in hematopoietic progenitor stem cells in the peripheral blood. The patient achieved a complete engraftment following two cycles of high-dose chemotherapy (paclitaxel, ifosfamide, carboplatin, etoposide), with the support of hematopoietic progenitor stem cells; the patient showed discrete tolerability to the treatment. At biochemical control, the ß-human chorionic gonadotropin value decreased from 86 to less than 1.2 mUI/ml and total body PET-CT scan showed a complete response to chemotherapy. According to this experience, we believe that in patients with advanced germ cell cancer, it is essential to explore the possibility of the use of high-dose chemotherapy to induce a stable and permanent response; in this context, plerixafor, with the support of granulocyte colony-stimulating factors, may be an innovative option for satisfactory mobilization during high-dose chemotherapy protocols.

An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia.

Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. This phase 2 study determined FCC efficacy and safety in relapsed/refractory CD52(+) B-CLL after ≥ 1 line of treatment. From January 2005 through June 2008, up to 6 courses of oral fludarabine 40 mg/m² per day, oral cyclophosphamide 250 mg/m² per day, and subcutaneous alemtuzumab (Mab-Campath) 10 mg (increased to 20 mg after first 10-patient cohort) were administered days 1 to 3 every 28 days. The primary objective was overall response rate (ORR); secondary objectives included response duration, time to disease progression, and safety and tolerability. ORR was 67% in 43 patients; 30% achieved complete response. ORR significantly improved with 1 versus ≥ 2 prior therapies (P = .018), and without versus with previous monoclonal antibody treatment (P = .003). Median progression-free survival was 24.4 months, not reached in patients achieving complete response. Median overall survival was 33.6 months. Myelosuppression was the most common adverse event, with a low percentage of cytomegalovirus reactivations and manageable infections. However, close vigilance of opportunistic infections is warranted. FCC provides effective immunotherapy in relapsed/refractory CLL, including in patients with poor-risk prognostic factors.

High-risk fludarabine-pretreated B-cell chronic lymphocytic leukemia's high response rate following sequential DHAP and alemtuzumab administration though in absence of molecular remission.

B-CLL patients with resistant/relapsed disease or adverse prognostic factors at presentation are suitable for alternative treatments. In the present pilot study we investigated a novel intensive chemo-immunotherapy approach for high-risk, fludarabine pretreated patients. Ten patients with resistant/relapsed, advanced stage BCLL were included. Age was 37-60 yr (median 53). All but one had an unmutated IgVH status. The treatment schedule included debulking with two DHAP courses followed by alemtuzumab (30 mg, eight doses), followed by peripheral blood progenitor cell (PBPC) mobilization with intermediate/high-dose cyclophosphamide and by autografting after high-dose mitoxantrone+L-Pam. The DHAP-alemtuzumab combination was highly effective. Eight patients out of 10 responded to DHAP, with a single complete remission. Following alemtuzumab, the number of overall responses increased to nine, and the complete remissions to five. After alemtuzumab PB double-positive clonal CD5+/CD19+ lymphocytes dropped, with median purification rate 99.95%. Owing to poor PBPC mobilization, only five patients underwent autografting, and three of these experienced post-graft recurrence. The six patients entering complete remission were free of disease 3-23 mo after study entry, and three of them were still in remission at 3, 7, and 22 mo. However, molecular evaluation regularly revealed persistence of minimal residual disease, both in all PBPC collections tested and in post-treatment follow-up samples. The use of DHAP/alemtuzumab appears useful to re-induce disease remission in relapsed/refractory, high-risk B-CLL patients. However, the addition of autograft was not usually feasible and of questionable clinical use. Other strategies should thus be considered for remission maintenance.