Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.

Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.

Plerixafor enables successful hematopoietic stem cell collection in an extensively pretreated patient with testicular cancer.

Plerixafor is a reversible CXCR4 antagonist that leads to a rapid release of hematopoietic stem and progenitor cells (HPSCs) from the bone marrow into the peripheral blood by interfering with the CXCL12-CXCR4 interaction. Based on two multicenter phase III studies, plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) was approved by the Food and Drug Administration for autologous HPSC mobilization in patients with multiple myeloma and non-Hodgkin's lymphoma. We report the case of a 26-year-old man with testicular cancer who was extensively pretreated and failed to mobilize a sufficient number of HPSCs after cytotoxic chemotherapy and the administration of G-CSF and pegylated G-CSF (PEG-G-CSF). Using a combination of plerixafor, G-CSF and PEG-G-GSF after chemotherapy, a sufficient number of HPSCs could be collected for the support of 3 sequential high-dose therapies. The patient achieved a complete and uncomplicated engraftment following each cycle of HPSC-supported high-dose therapy. Patients suffering from advanced germ cell cancer may be another group that benefits from the use of plerixafor, which to date has only been approved for the treatment of multiple myeloma and lymphoma. To our knowledge, this is the first case report of successful mobilization of HPSCs with plerixafor in a patient with testicular cancer.

Predictive factors for successful salvage high-dose therapy in patients with multiple myeloma relapsing after autologous blood stem cell transplantation.

For patients with relapsed or refractory multiple myeloma (MM) treated with a prior high-dose therapy (HDT) followed by autologous peripheral blood stem cell transplantation (PBSCT), the reapplication of HDT is a widely used salvage strategy. In this retrospective study, we report on 55 patients who were treated with salvage HDT at our institution. The conditioning regimen consisted of melphalan 200 mg/m(2) (27%), melphalan 140 mg/m(2) and busulfan 12 mg/kg body weight (40%), or melphalan 200 mg/m(2) and bortezomib 1.3 mg/m(2) (33%). Treatment-related mortality was 5% and response rates were as follows: 9% complete remission, 9% very good partial remission, 56% partial remission, 11% minimal response + stable disease, and 4% progressive disease (5% not assessable). Toxicity was moderate and the median event-free (EFS) and overall survival (OS) were 14 months and 52 months, respectively. The different conditioning regimens did not result in differences in terms of remission rates, EFS and OS, or toxicity. In multivariate analysis a duration of remission of more than 12 months after the first transplant was the only predictive factor for both EFS (p < 0.0001) and OS (p = 0.0001). In conclusion, salvage HDT followed by autologous PBSCT is an effective treatment option for patients with relapsed or refractory MM, while patients with an early relapse after their first transplant do not benefit from this treatment modality.

Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors.

BACKGROUND: Treatment with natalizumab, an antibody blocking the α4-integrin, is associated with increased numbers of circulating CD34+ cells in the peripheral blood of patients with multiple sclerosis. OBJECTIVE: To determine whether natalizumab mobilizes CD34+ cells from or inhibits homing to the bone marrow (BM). DESIGN: Fifty-two patients with relapsing-remitting multiple sclerosis treated with natalizumab were included. Flow cytometric analyses; polymerase chain reaction assays for JC (John Cunningham) virus DNA detection; and adhesion, migration, and apoptosis assays of immunomagnetically enriched peripheral blood and BM CD34+ cells were conducted. A comparison was made with CD34+ cells from granulocyte colony-stimulating factor-mobilized peripheral blood or steady-state BM of age- and sex-matched healthy donors. RESULTS: We found adhesion and migration of peripheral blood-derived CD34+ cells to be reduced. In BM aspirates from natalizumab-treated patients, the cellularity, the proportion, and the adhesive capacity of CD34+ cells were normal. The JC virus was undetectable. CONCLUSIONS: Natalizumab mediates an increase in circulating CD34+ cells by interfering with homing to the BM. Thus, CD34+ cells appear unlikely to represent a source mobilizing JC virus out of the BM in patients treated with natalizumab.