Subject(s)
Antineoplastic Agents/therapeutic use , Drug Substitution , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Imatinib Mesylate/therapeutic use , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
Myeloproliferative neoplasms (MPN) are chronic disorders that can sometimes evolve into accelerated or leukemic phases. We retrospectively identified 122 patients with such blastic phases. The overall median survival was four months: 10.2 months for patients treated with intensive treatments compared to three months for best supportive care (p = .005). Azacytidine, intensive chemotherapies, or allogeneic stem cell transplantation gave the highest median survivals with 9, 10.2, and 19.4 months, respectively. Accelerated phases (AP) had a longer median survival compared to acute leukemia (4.8 months vs. 3.1 months; p = .02). In this retrospective and observational study, we observe that the longest survivals are seen in patients eligible for intensive treatments. Azacytidine shows interesting results in patients non-fit for intensive chemotherapy. Supportive care should probably be restricted to elderly patients and those with unfavorable karyotype. An early diagnosis of AP could also result in a better survival rate.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/therapeutic use , Blast Crisis/therapy , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Adult , Aged , Aged, 80 and over , Blast Crisis/mortality , Cross-Sectional Studies , Female , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Palliative Care/methods , Retrospective Studies , Survival Analysis , Survival Rate , Transplantation, Homologous , Treatment OutcomeSubject(s)
Chromosome Deletion , Chromosomes, Human, Pair 5 , Mutation , Myelodysplastic Syndromes/genetics , Tumor Suppressor Protein p53/genetics , Disease Progression , Female , Humans , Lenalidomide/therapeutic use , Male , Middle Aged , Myelodysplastic Syndromes/classification , Myelodysplastic Syndromes/diagnosis , PrognosisABSTRACT
Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.
Subject(s)
Immunoglobulin Light Chains/blood , Immunoglobulin Light Chains/urine , Multiple Myeloma/blood , Multiple Myeloma/urine , Adult , Consolidation Chemotherapy , Humans , Induction Chemotherapy , Middle Aged , Multiple Myeloma/drug therapy , Predictive Value of Tests , Proportional Hazards Models , Reference Standards , Survival AnalysisABSTRACT
The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide-dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27.
