Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Enterovirus Infections/diagnosis , Enterovirus/isolation & purification , Meningoencephalitis/virology , Adult , Enterovirus/genetics , Enterovirus Infections/cerebrospinal fluid , Enterovirus Infections/etiology , Female , Humans , Lymphoma, Follicular/drug therapy , Meningoencephalitis/etiologyABSTRACT
RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.
Subject(s)
Erythrocyte Transfusion , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Adult , Aged , Aged, 80 and over , Australia , Cause of Death , Combined Modality Therapy , Disease Management , Erythrocyte Transfusion/methods , Female , Germany , Humans , Incidence , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Prognosis , Proportional Hazards Models , Registries , Reproducibility of Results , Treatment Outcome , Young AdultABSTRACT
To improve complete remission (CR) rates by reducing toxicity and enhancing delivery, we created a modified hyper-CVAD/MA regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone/methotrexate, cytarabine) by reducing the cytarabine dose (3 g/m2 to 2 g/m2) and number of cycles (eight to six). We conducted a phase II trial in the pre-rituximab era in the intermediate-high international prognostic index (IPI) (≥2) de novo diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) (ACTRN12605000105640). CR rates were compared with reported IPI-stratified rates. Sixty-three patients (n = 26 PTCL; n = 37 DLBCL) were evaluated; median follow-up of 30 months. CR rates for PTCL and DLBCL patients were 46% and 49%, respectively, similar with reported CR rates with CHOP-like chemotherapy (p = .6). Of the patients, 51 (81%) experienced ≥1 unplanned hospital admission; only 41 (65%) completed six cycles. The cytarabine modifications did not prevent significant toxicity. Modified hyper-CVAD/MA resulted in similar outcomes to CHOP-like chemotherapy in aggressive lymphomas and was associated with significant toxicity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, T-Cell, Peripheral/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cause of Death , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Disease Progression , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/mortality , Male , Middle Aged , Recurrence , Remission Induction , Survival Analysis , Treatment Outcome , Vincristine/adverse effects , Vincristine/therapeutic use , Young AdultABSTRACT
Treatment of chronic myeloid leukemia (CML) patients using imatinib alone is unlikely to be curative. The challenges in the era of imatinib are to prevent the emergence of imatinib resistance and to identify the most effective alternative approaches for patients who lose imatinib responsiveness. This review describes the possible strategies to overcome imatinib resistance in CML patients based on the current understanding of the action of imatinib and mechanisms of its resistance. The useful laboratory tests to study imatinib resistance and a current Australian CML study employing imatinib dose intensification and sequential combination therapy for newly diagnosed patients are also outlined.
Subject(s)
Antineoplastic Agents/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzamides , Drug Resistance, Neoplasm , Humans , Imatinib Mesylate , Piperazines/administration & dosage , Pyrimidines/administration & dosageSubject(s)
Adjuvants, Immunologic/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Combined Modality Therapy , Humans , Lenograstim , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Recombinant Proteins/therapeutic use , Transplantation, AutologousABSTRACT
Transfusion is a 'vein-to-vein' process. The blood supply in Australia is extremely safe in terms of viral risk, although a 'zero risk' blood transfusion is never possible. Safe transfusion practice continues to rely on highly-trained and experienced staff undertaking procedures correctly, in robust hospital systems within a safety and quality framework that includes an adverse event reporting system. Such a reporting system should work to enhance any hospital system where weaknesses or deficiencies are found. Further information on national guidelines and other aspects of transfusion in Australia can be found at: www.anzsbt.org.au/publications and www.transfusion.com.au. A transfusion administration checklist for nurses can be downloaded from: http://www.transfusion.com.au/Resourc eLibrary/resource_safety_2 .asp