The pharmacokinetics and pharmacodynamics of busulfan when combined with melphalan as conditioning in adult autologous stem cell transplant recipients.

Busulfan (Bu) is an alkylating agent widely used in conditioning regimes prior to stem cell transplantation (SCT), most commonly in combination with cyclophosphamide (Bu-cy) or fludarabine (Bu-flu) as myeloablative conditioning prior to allograft or with high-dose melphalan (Bu-mel) prior to autologous SCT. Despite many decades of Bu use, initially orally but now intravenously (IV), a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) data exists to inform evidence-based guidelines as how best to balance the efficacy and toxicity of this agent. This is a non-randomized retrospective real-world study at three hospitals investigating the role of PK guidance in dosing Bu in the setting of IV Bu-mel autologous SCT.

The effect of folinic acid on methylenetetrahydrofolate reductase polymorphisms in methotrexate-treated allogeneic hematopoietic stem cell transplants.

This study examined the contribution single nucleotide polymorphisms (SNPs) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have on clinical outcomes in hematopoietic stem cell transplant patients treated with the antiproliferative drug methotrexate. Two common SNPs, 677C>T and 1298A>C, were genotyped by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) from samples obtained from patient DNA samples. Eleven clinical outcomes including survival and graft-versus-host disease (GVHD) were assessed against donor and recipient MTHFR genotypes against pretransplantation variables.

Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre-transplant FDG-PET scan following salvage chemotherapy.

The utility of ([18F])fluoro-2-deoxy- d-glucose positron-emission tomography (FDG-PET) for predicting outcome after autologous stem cell transplantation (ASCT) for diffuse large B cell lymphoma (DLBCL) is uncertain - existing studies include a range of histological subtypes or have a limited duration of follow-up. Thirty-nine patients with primary-refractory or relapsed DLBCL with pre-ASCT PET scans were analysed. The median follow-up was 3 years.

Genetic heterogeneity of granulocytes for the JAK2 V617F mutation in essential thrombocythaemia: implications for mutation detection in peripheral blood.

Aims: The molecular pathogenesis of essential thrombocythaemia (ET) is heterogeneous. We aimed to determine the relative sensitivity of four separate molecular assays used to detect the presence of the JAK2 V617F mutation in peripheral blood from patients with essential thrombocythaemia and related myeloproliferative disorders.

Methods: Purified granulocytes from 60 patients were analysed for the presence of the JAK2 V617F mutation by direct sequencing, denaturing high-performance liquid chromatography (DHPLC), allele-specific polymerase chain reaction (PCR) and allele-specific enrichment.