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Biomedical subjects

Martin Bornhauser

Publications and source records attributed to Martin Bornhauser.

7 recordsLinked to original sources
PubMed2006

Haploidentical allogeneic hematopoietic cell transplantation in adults with reduced-intensity conditioning and CD3/CD19 depletion: fast engraftment and low toxicity.

OBJECTIVE: CD3/CD19 depletion may improve engraftment and immune reconstitution after haploidentical hematopoietic cell transplantation (HHCT) as grafts not only contain CD34+ stem cells but also CD34- progenitors and natural killer, dendritic, and facilitating cells. PATIENTS AND METHODS: Ten consecutive patients received HHCT with CD3/CD19-depleted grafts. Reduced-intensity conditioning was performed with fludarabine (150-200 mg/m2), thiotepa (10 mg/kg), melphalan (120 mg/m2), and OKT-3 (5 mg/day, day -5 to +14) without additional posttransplant immunosuppression. Diagnoses were AML (n = 4), ALL (n = 3), NHL (n = 2), and multiple myeloma (n = 1). All patients were "high risk" with refractory disease or relapse after preceding HCT. The CD3/CD19-depleted haploidentical grafts contained a median of 7.8 x 10(6) (range, 5.2-17 x 10(6)) CD34+ cells/kg, 5.5 x 10(7) (range, 0.02-8.6 x 10(7)) CD56+ cells/kg, and 2.0 x 10(4) (range, 0.006-44 x 10(4)) CD3+ T cells/kg. Engraftment was rapid with median time to greater than 500 granulocytes/microL of 13 (range, 11-17) days, greater than 20,000 platelets/microL of 11 (range, 8-16) days, and full donor chimerism after 2 weeks in all patients. Six cases of grade II GVHD occurred. One patient, who received the highest T cell dose, developed lethal grade IV GVHD. Treatment-related mortality in the first 100 days was 3/10 (30%) with one death each due to idiopathic pneumonia syndrome, GVHD, and CMV disease. Two patients died after day 100, one due to relapse and one with systemic adenoviral infection. Overall survival is 5/10 patients (50%) with a median follow-up of 435 (range, 229-814) days. CONCLUSION: This regimen is promising in high-risk patients lacking a suitable donor, and a prospective phase I/II study is ongoing.

Adult↗
PubMed2005

Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase 2 study on reduced-intensity myeloablative conditioning with fractionated 8-Gy total body irradiation (TBI) and fludarabine (120 mg/m2). Patients received mobilized peripheral blood stem cells (n = 68) or bone marrow (n = 3) from siblings (n = 39) or unrelated donors (n = 32). Thirty-six patients received a transplant in complete remission (CR) and 35 had untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20-66 years). Sustained engraftment was attained in all evaluable patients. With a median follow-up of 25.9 months (range, 3.7-61.2 months) in surviving patients, probabilities of overall survival for patients who received a transplant in CR and non-CR were 81% and 21% at 2 years, respectively. Relapse-free survival rates were 78% and 16%. The cumulative incidence of nonrelapse mortality (NRM) in CR patients was 8% at 2 years and beyond but amounted to 37% at 2 years in non-CR patients. Outcome data in this poor-risk population indicate that allogeneic HSCT from related or unrelated donors with 8-Gy TBI/fludarabine conditioning is feasible with low NRM and preserved antileukemic activity in AML patients in first or later CR.

Adult↗
PubMed2005

Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors.

BACKGROUND AND OBJECTIVES: Short-term treatment with granulocyte colony-stimulating factor (G-CSF) has been established as the standard regimen for mobilizing allogeneic peripheral blood progenitor cells (PBPC) from healthy donors. The pegylated form of filgrastim (pegfilgrastim) has a longer elimination half-life because of decreased serum clearance and might be a convenient alternative for stem cell mobilization. DESIGN AND METHODS: Twenty-five family (n=15) or unrelated (n=10) healthy donors received a single-dose of 12 mg pegfilgrastim for mobilization of allogeneic PBPC. Donors with inadequate mobilization (blood CD34+ cells <or=5/microL on day 3 or <or=20/mL on day 4) were given additional daily doses of 10 mg/kg conventional filgrastim. Leukapheresis was planned to start on day 5. RESULTS: All harvests were completed successfully. In 20 out of 25 donors (80 %) only a single apheresis was necessary. Additional non-pegylated filgrastim had to be given to only one 74-year old family donor. The maximum concentration of circulating CD34+ cells occurred on day 5 (median 67/microL, range 10-385/mL). The median yield of CD34+ cells was 9.3 (range 3.2-39.1)x10(6)/kg of the recipient's body weight. The median number of T cells in the apheresis products was 3.9 (range 2.7-10.8)x10(8)/kg. Bone pain, headaches and transient elevations of alkaline phosphatase and lactate dehydrogenase were the main adverse events. INTERPRETATION AND CONCLUSIONS: The study shows that collection of allogeneic PBPC after administration of a single dose of pegfilgrastim is feasible. The toxicity profile, graft composition and impact on the recipients' outcome need further investigation.

Adult↗
PubMed2003

CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid.

Imatinib mesylate (STI571) is a very effective treatment option for Ph(+) chronic myeloid leukemia (CML) in chronic phase. Secondary treatment failures have mostly been observed in patients with advanced stages of disease. We report the case of a patient who unexpectedly experienced blast crisis of the central nervous system although having achieved complete cytogenetic remission in the bone marrow. The levels of STI571 and its metabolite N-desmethyl STI were 40-fold lower in the cerebral spine fluid than in plasma. The risk of CNS disease has to be kept in mind when patients with CML in chronic phase who are at an increased risk for blastic transformation are treated with imatinib mesylate.

Antineoplastic Agents↗
PubMed2003

Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells.

A regimen of busulfan and cyclophosphamide is standard therapy before transplantation of allogeneic hematopoietic stem cells in patients with chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). The clinical trial reported here was undertaken to test the hypothesis that fludarabine can replace cyclophosphamide in this regimen and facilitate donor engraftment with reduced toxicity. The conditioning regimen consisted of 30 mg/m2 intravenous fludarabine daily from day -9 to day -6, and oral busulfan given at 1 mg/kg 4 times a day every 6 hours from day -5 to day -2, with doses adjusted to target plasma levels of 900 +/- 100 ng/mL at steady state. Cyclosporine and methotrexate were used for prophylaxis for graft-versus-host disease. Enrolled were 42 patients with high-risk CML (n = 4) or MDS (n = 38). The median patient age was 52 years (range, 12-65 years). Mobilized blood stem cells were obtained from HLA-compatible siblings (n = 16) or unrelated donors (n = 26). Engraftment was achieved in all patients, and the day-100 regimen-related mortality was 7%. With a median follow-up of 18 months (range, 13-27 months), the probabilities of overall survival, disease-free survival, and nonrelapse mortality were 42.4%, 34.9%, and 24%, respectively. These data indicate that the combination of fludarabine and targeted busulfan is sufficiently immunosuppressive to facilitate engraftment of blood stem cells from HLA-matched siblings and unrelated donors. Based on these encouraging results, further studies of fludarabine and targeted busulfan are warranted in standard-risk patients.

Adolescent↗