Donald Gabriel

Utility of obtaining blood cultures in febrile neutropenic patients undergoing bone marrow transplantation.

Infection remains an important cause of morbidity and mortality after bone marrow or stem cell transplantation. To evaluate the role of obtaining blood cultures for intermittent or persistent fever in neutropenic patients on antibiotic therapy, we performed a retrospective chart review of 196 consecutive patients admitted to the Bone Marrow Transplant Unit at the University of North Carolina Hospitals from 1995 to 1998. From the cohort of 196 patients, 154 patients developed neutropenic fever. The initial blood culture was positive in 16 of 145 patients during the first fever episode giving a prevalence of 11%. From the total of 109 patients that had blood cultures drawn after day 1 of fever, five patients had blood cultures positive for a pathogen, a prevalence of 4.6%. In only one patient, did blood cultures drawn after day 1 identify an organism not present on day 1 (prevalence 0.9%). After reviewing the results in the first 105 patients, we changed our timing of collection of blood cultures. Forty-nine patients were treated in this manner and we found that the mean number of blood cultures decreased from 9.2 to 4.7 per patient without a change in the frequency of infectious complications or length of hospitalization. Bone Marrow Transplantation (2000) 26, 533–538.

Chemomobilization with Etoposide is Highly Effective in Patients with Multiple Myeloma and Overcomes the Effects of Age and Prior Therapy

The optimal mobilization strategy prior to autologous stem cell transplantation for patients with multiple myeloma remains unclear. Mobilization with cytokines alone appears to yield suboptimal results in older patients as well as patients who have received prior lenalidomide. To avoid the marked cytopenias and risks of hemorrhagic cystitis associated with the administration of cyclophosphamide, we investigated the efficacy and safety of chemomobilization with an intermediate dose etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and granulocyte-colony stimulating factor (G-CSF) (5 μg/kg twice daily from day +3 through the final day of collection). We reviewed our institutional experience with 152 myeloma patients mobilized with this regimen. The addition of VP-16 to G-CSF resulted in successful mobilization in 100% of patients, including 143 (94%) who collected successfully in a single day. A total of 99% of patients, including those with prior XRT and/or prior lenalidomide or thalidomide therapy, collected at least 5 × 10(6) cells/kg in 1 or 2 days of apheresis, and the median total number of CD34(+) cells collected in the entire population was 12 × 10(6) cells/kg. Collection was predictable, with 61% of patients collecting on day +11, and the rest between days +7 and +13. There were no variables, including age, prior imid exposure, radiation therapy, or total amount of prior therapy that were associated with suboptimal mobilization. Adverse effects of the regimen included supportive transfusions required in 31 (20%) patients, and fevers requiring hospitalization or intravenous antibiotics in 26 (17%) patients. VP-16 and G-CSF appears to be a safe and effective mobilization regimen for patients with multiple myeloma undergoing autologous stem cell transplantation, producing excellent stem cell yield with the majority of patients requiring 1 day of apheresis.

CD34 + selection of hematopoietic blood cell collections and autotransplantation in lymphoma: overnight storage of cells at 4°C does not affect outcome

The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 μg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4°C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). neutrophil recovery >500u2009×u2009109/l occurred a median of 11 days (range 9–16 days) in the overnight storage group compared to 10.5 days (range 9–21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7–43) days in the overnight storage group vs 13.5 (range 8–35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4°C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559–566.

Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy [3]

Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy

Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto-SCT

The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375u2009mg/m2 on days +1 and +2) and G-CSF (5u2009μg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 106 CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 106 cells in ⩽2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were

Usefulness of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in predicting outcomes for adolescents and young adults with hematologic malignancies undergoing allogeneic stem cell transplant†

14u2009923 for good mobilizers and

B Cells from Patients with Chronic GVHD Signal Via the Akt-Driven Survival and Metabolic Fitness Pathway

27u2009044 for poor mobilizers (P<0.05). Using our data, we performed a ‘break-even’ analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents.

Identification of an AUC of 7603 Umol∗Min/Hr Per Day X 4 Days as the Maximum Tolerated Dose (MTD) of IV Continuous Infusion (CI) Busulfan (BU) with Fixed Dose Fludarabine (FLU) in A Pharmacokinetically-Based Dose Phase I Study in Patients (PTS) with Hematologic Malignancies Undergoing Allogeneic Stem Cell Transplantation

The HCT‐CI helps to predict non‐relapse mortality (NRM) and overall survival (OS) in allogeneic hematopoietic cell transplantation (HCT) recipients. The usefulness of this index in a younger, adolescent and young adult (AYA) population is unclear.