Wolfram Poenisch

BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning

Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2 Gy total-body irradiation in combination with (n=14) or without (n=3) fludarabine 3 × 30 mg/m2 (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 × 5 mg (n=2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman® RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.

Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study

We prospectively evaluated the activity and tolerance of lenalidomide-dexamethasone in 35 patients with acute light chain-induced renal failure. The lenalidomide dose was adapted to the estimated glomerular filtration rate and dexamethasone was given at high dose in cycle one and at low dose thereafter. Four patients died within the first two cycles, and five discontinued therapy leaving 26 patients for the per-protocol analysis. Responses were observed in 24/35 (68.6%) patients of the intent-to-treat population. Complete response was noted in seven patients (20%), very good partial response in three patients (8.6%), partial response in 14 patients (40%), and minimal response in one patient (2.9%). Renal response was observed in 16 (45.7%) patients: five (14.2%) achieved complete, four (11.4%) partial and seven (20%) minor renal responses. Five of 13 patients who were dialysis dependent at baseline became dialysis independent. The median time to myeloma and to renal response was 28 days for both parameters, while the median time to best myeloma and best renal response was 92 and 157 days, respectively. The median estimated glomerular filtration rate increased significantly in patients with partial response or better from 17.1 mL/min at baseline to 39.1 mL/min at best response (P=0.001). The median progression-free and overall survival was 5.5 and 21.8 months, respectively, in the intent-to-treat population and 12.1 and 31.4 months, respectively, in the per-protocol group. Infections, cardiotoxicity, anemia and thrombocytopenia were the most frequent toxicities. In conclusion, the lenalidomide-dexamethasone regimen achieved rapid and substantial myeloma and renal responses. The trial was registered under EUDRACT number 2008-006497-15.

Primary mediastinal large B cell lymphoma: Frontline treatment with an alternating chemotherapy regimen based on high dose methotrexate - A single institution experience

Background and Aims: In this retrospective analysis, we report our experience with the high-dose methotrexate-based chemotherapy B-ALL protocol of the German ALL study group followed by consolidative mediastinal radiotherapy in patients with adult primary mediastinal large B-cell lymphoma (PMLBCL) as a single-center trial. Setting and Design: Nineteen patients with newly diagnosed/untreated PMLBCL who were treated between June 1999 and May 2013 were included. Patients received a high-dose methotrexate protocol consisting of six cycles. Materials and Methods: Patients received thrice block A [day 1: methotrexate 1,500 mg/m2 for 24 h; days 1-5: ifosfamide 800 mg/m2; days 4-5: VM-26 100 mg/m2 and ara-C 2x150 mg/m2 (bid); days 1-5: dexamethasone 10 mg/m2 p.o.] and thrice block B [day 1: vincristine 2 mg i.v., MTX as in block A; days 1-5: cyclophosphamide 200 mg/m2; days 4-5: adriamycin 25 mg/m2; days 1-5: dexamethasone 10 mg/m2 p.o.] applied alternatively every 3 weeks. Results: After chemotherapy five patients achieved CR, nine patients CRu and four patients PR. The restaging procedures after consolidation radiotherapy showed an overall response rate of 95% (9 CR and 9 CRu). With a median follow-up of 56 months, progression free survival and overall survival at 60 months were 88%. The most common grade 3/4 hematological toxicities were leukocytopenia and neutropenia (100%), thrombocytopenia (95%), and anemia (63%). Conclusion: Our data suggest that the current high-dose methotrexate-based chemotherapy protocol followed by consolidation mediastinal radiotherapy in patients with adult PMLBCL is feasible, effective, and moderately tolerated.