Acquisition of genomic events leading to lymphoblastic transformation in a rare case of myeloproliferative neoplasm with BCR-JAK2 fusion transcript.

We report a case of myeloproliferative neoplasm (MPN) with an atypical t(9;22;15)(p24;q11;q21) translocation, leading to a BCR-JAK2 fusion, associated with a trisomy of chromosome 8 in clonal evolution at karyotype. Patient's evolution was marked by an aggressive clinical course with rapid progression to blast phase within the first year after diagnosis. Examination of matched chronic phase and blast crisis samples by SNP-array karyotyping identified secondary acquired cryptic genetic events at the time of lymphoblastic transformation, including biallelic IKZF1 alteration and EBF1 and CDKN2A/B codeletions. This case is the first report describing acquisition of secondary genetic events leading to acute lymphoblastic progression in a rare MPN with BCR-JAK2 fusion.

Frontline treatment in multiple myeloma patients not eligible for stem-cell transplantation.

Melphalan-prednisone-thalidomide (MPT) currently appears to be the treatment of choice for a large proportion of elderly patients ineligible for autologous stem-cell transplantation (ASCT). It seems certain that in the near future melphalan-prednisone-Velcade (MPV) and melphalan-prednisone-lenalidomide (MPR) will also be proved superior to melphalan-prednisone (MP), thus providing three therapeutic options (MPT, MPV and MPR) in this patient group with multiple myeloma (MM). These therapeutic options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel therapies have somewhat different toxicity profiles. MP would be appropriate for only a minority of patients with poor performance status and/or significant comorbidities, such as severe neuropathy or a contraindication to anticoagulants. Questions regarding the relative efficacy of melphalan-based regimens versus dexamethasone-based regimens (preferably with low-dose dexamethasone) will require randomized phase-III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated, especially in elderly patients.

Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning.

The purpose of this study was to evaluate the impact of enteral nutrition on early outcome of patients after myeloablative allogeneic stem cell transplantation (allo-SCT). From January 2001 to January 2003, 22 patients agreed to receive enteral nutrition via a nasogastric feeding tube; the remaining 23 patients received parenteral nutrition (n=22) or standard oral feeding (n=1). Early complications and factors influencing 100-day overall survival (OS) were investigated. Patients who received enteral nutrition developed less often acute-grade III/IV graft-versus-host disease (18%) than those who did not (35%) (P=0.011). In addition, this group showed lower mortality from infection during the first 100 days after transplantation. In multivariate analyses, only the absence of enteral nutrition was found to adversely influence 100-day OS with a hazard ratio of 8.3. Enteral nutrition is a safe and effective method for feeding allo-SCT patients. A randomized trial is warranted to confirm its advantage on early patient outcome.

An 18-case outbreak of drug-resistant Pseudomonas aeruginosa bacteriemia in hematology patients.

We retrospectively identified an outbreak of 18 episodes of P. aeruginosa bacteriemia in 17 patients with hematologic malignancies in 2004. All strains were ticarcillin I/R, 77% ciprofloxacin I/R, 72% ceftazidime I/R, 72% amikacin I/R and 50% imipenem I/R. The outbreak was multiclonal. Colistin was employed for documented therapy in ten cases including seven in which it was the only active drug. Outcomes were resolution of infection in 12 out of 18 episodes (67%), and death in six cases, five (25%) of which were attributable to the infection. Colistin was useful even in highly resistant strains and the efficacy of antibacterial therapy was similar (57%)in bacteriemia due to strains only susceptible to colistin.

Factors predicting molecular and cytogenetic response in chronic myeloid leukemia patients treated with imatinib.

We studied 94 clinically heterogeneous chronic myeloid leukemia (CML) patients and found that the duration of treatment with interferon-alpha (IFN-alpha) prior to imatinib therapy may not improve response to imatinib for patients in chronic phase but a shorter period between CML diagnosis and the initiation of imatinib is predictive for a better molecular response to therapy (p<0.05).

Serum immunoglobulin free light chain correlates with tumor burden markers in Waldenstrom macroglobulinemia.

The serum IgM level has been utilised as a marker of tumor progression and to assess response to therapy in patients with Waldenstrom macroglobulinemia (WM). However, there are many limitations to the IgM protein level. The objective of this study was to evaluate the association of known tumor burden markers and prognostic factors with serum free light chain (sFLC) in 98 patients with WM. We demonstrated that sFLC measurement accurately differentiated IgM-MGUS compared with WM reflecting a measurement of tumor burden. In univariate and multivariate analysis, median sFLC at the cut-off at 60 mg/L was higher for WM patients with low hemoglobin and high beta2M, when we applied the WM-IPSS cut-offs, but showed no association with IgM level. This study demonstrates that sFLC is a new marker in WM disease. Further analysis is required to prospectively study the role of sFLC in monitoring response to therapy and as a prognostic marker in WM patients.