Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Treatment of burn injury by cellular repair.

Burn injury leads to a direct damaging effect on cells, disrupting the assembly of the cell and denaturing proteins. Although modern medicine has significantly improved the survival of burn victims, a method to treat injury at the cellular level is presented. In particular, the cell membrane is most vulnerable to heat injury. Copolymer surfactants have been shown to repair the cell membrane, and agents such as poloxamer 188 have demonstrated this effect in numerous studies. Furthermore, copolymer surfactants have been shown to act as molecular chaperones, allowing denatured proteins to regain their native confirmation. Pharmaceutical agents may be developed to repair the cell membrane and refold proteins, mimicking endogenous repair mechanisms and salvaging cells that would otherwise be lost.

Copper deficiency mimicking myelodysplastic syndrome.

Copper deficiency is a rare cause of pancytopenia that may be mistaken for myelodysplastic syndrome. Cytoplasmic vacuolization in erythroid and myeloid precursors is found on bone marrow examination. Patients with a history of abdominal surgery who present with anemia and neutropenia with dysplastic changes should have copper levels checked.

Bortezomib (Velcade), rituximab, cyclophosphamide, and dexamethasone combination regimen is active as front-line therapy of low-grade non-Hodgkin lymphoma.

OBJECTIVE: To evaluate the efficacy and toxicity of the combination of VRCD (velcade/rituximab/cyclophosphamide/dexamethasone) in chemotherapy-naïve low-grade non-Hodgkin lymphoma or patients with transplantation-ineligible mantle cells. METHODS: The patients were treated with velcade, at 1.6 mg/m(2), on days 1, 8, 15, and 22 on every 35-day cycle. Rituximab was given at 375 mg/m(2) on the same days as velcade during cycle 1 and then only on day 1 in subsequent cycles. Dexamethasone was given orally at 40 mg on days 1, 2, 8, 9, 15, 16, 22, and 23. Cyclophosphamide was administered orally at 400 mg/m(2) on days 1-4. The patients had to meet criteria to initiate therapy and had to demonstrate adequate performance status and organ function. RESULTS: Twelve patients were enrolled, after which the study was closed due to a lack of funding. The median age was 68 years (37-83 years), with 83% having stage III/IV disease. Five patients had marginal zone, 4 had follicular, 2 had small lymphocytic, and 1 had mantle cell histologies. The overall response rate was 90% (complete response, 54%). At a median follow-up of 22 months, 9 (75%) patients remain alive, and the median time to progression has not been reached. A third of the patients required dose reductions after a median of 6.5 cycles. No grade 3 or 4 peripheral neuropathy was witnessed. CONCLUSIONS: Although the number of studied patients is small, VRCD appears safe and active as front-line therapy for low-grade non-Hodgkin lymphoma. Further studies are justified.

Biologic agent activity in chronic lymphocytic leukemia: a framework for future therapies.

The previous decade has witnessed remarkable advances in our understanding and treatment of chronic lymphocytic leukemia. Chemoimmunotherapy has provided patients with unprecedented remission rates and has improved survival compared to chemotherapy alone. However, the availability of targeted therapies and monoclonal antibodies argues for exploring non-cytotoxic and biologic regimens for this disease. In this article, we review available targeted and non-chemotherapeutic agents for CLL, attempting to position these therapies in the treatment paradigm of CLL in the era of risk stratification as we move forward.