Severe and prolonged myelosuppression during concomitant temozolomide and radiotherapy treatment in a patient with glioblastoma multiforme

Aims: We describe the case of a patient with glioblastoma (GBM) who developed severe and prolonged myelosuppression during concomitant daily temozolomide (TMZ) and radiotherapy (RT) treatment. Analysis of polymorphisms in genes correlated with TMZ-induced myelotoxicity was also performed. Presentation of the Case: A 67–year-old man with diagnosis of GBM undergoing concomitant RT-TMZ treatment developed severe and prolonged pancytopenia that led to discontinuation of TMZ and required frequent platelet and red cells transfusions. Analysis of single nucleotide polymorphisms (SNPs) in the genes NAD(P)H dehydrogenase, quinone 1 (NQO1) and glutathione S-transferase pi 1 (GSTP1) was carried out. Both SNPs were found to be wild-type. Discussion: TMZ is an oral alkylating agent used for the treatment of glioblastoma. TMZ is usually considered well tolerated and safe, with nausea and mild myelosuppression being the most common side effects. However, severe haematologic adverse events have been also reported. Recently, there has been growing interest in gene polymorphisms that might be associated with an increased risk of hematologic toxicity. Conclusion: Myelosuppression is a side effect that can occur relatively early during concomitant TMZ treatment and can negatively impact on patient’s quality of life. Further studies are warranted to find out a correlation between genetic factors and the occurrence of severe hematologic toxicity

A population-based study on myelodysplastic syndromes in the Lazio Region (Italy), medical miscoding and 11-year mortality follow-up. The Gruppo Romano-Laziale Mielodisplasie experience of retrospective multicentric registry

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival

Azacitidine for the treatment of lower risk myelodysplastic syndromes : a retrospective study of 74 patients enrolled in an Italian named patient program.

BACKGROUND: Azacitidine induces responses and prolongs overall survival compared with conventional care regimens in patients who have high-risk myelodysplastic syndromes (MDS). However, limited data are available concerning the efficacy and safety of azacitidine in patients who have lower risk MDS. METHODS: The authors retrospectively evaluated 74 patients with International Prognostic Scoring System low-risk or intermediate 1-risk MDS, who received azacitidine on a national named patient program. At baseline, 84% of patients were transfusion-dependent, 57% had received erythropoietin, and 51% were aged >70 years. Azacitidine was administered subcutaneously for 5 days (n = 29 patients), 7 days (n = 43 patients), or 10 days (n = 2 patients) every month at a dose of 75 mg/m(2) daily (n = 45 patients) or at a fixed dose of 100 mg daily (n = 29 patients) and for a median of 7 cycles (range, 1-30 cycles). RESULTS: According to the 2006 International Working Group criteria, overall response rate (ORR) was 45.9%, including complete responses (10.8%), partial responses (9.5%), hematologic improvements (20.3%), and bone marrow complete responses (5.4%). The ORR was 51.6% in 64 patients who completed > or = 4 cycles of treatment. The median duration of response was 6 months (range, 1-30 months). After a median follow-up of 15 months, 71% of patients remained alive. A survival benefit was observed in responders versus nonresponders (94% vs 54% of patients projected to be alive at 2.5 years, respectively; P < .0014). The most common grade 3 or 4 adverse events were myelosuppression (21.6%) and infection (6.8%). CONCLUSIONS: The current results indicated that azacitidine may be a feasible and effective treatment for patients with lower risk MDS

Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence

Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136),TI with hemoglobin (Hb) >= 10 mg/dL (n = 88),or TI with Hb = 10 g/dL],108 months;TI [Hb <10 g/dL],77 months;TD, 44 months). Transfusion dependence also negatively impacted non-leukemic death rates. In the interventional part of the study, baseline Hb levels were found to correlate significantly with physical (R = 0.666, P = 0.035) and fatigue (R = 0.604, P = 0.049) QoL scores. Median physical QoL scores improved significantly after 12 weeks' treatment with lenalidomide (+12.5;P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide

Loss of CDKN1B induces an age‐related clonal hematopoietic disorder via Notch2 activity dysregulation

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