Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.     

Clinical Benefit-Risk Profile of Lenalidomide in Patients With Lower-risk Myelodysplastic Syndromes Without del(5q): Results of a Phase III Trial

BackgroundIn the phase III MDS-005 study of patients with lower-risk, non-del(5q) myelodysplastic syndromes, lenalidomide was associated with a higher rate of ≥ 8 weeks red blood cell transfusion independence (RBC-TI) compared with placebo, but also with a higher risk of hematologic adverse events (AEs).Patients and MethodsThis analysis evaluated the ratio of clinical benefit-risk in patients treated with lenalidomide or placebo, and assessed the effect of lenalidomide dose reductions on response. Clinical benefit was a composite endpoint defined as RBC-TI, transfusion reduction ≥ 4 units packed red blood cells, hemoglobin increase ≥ 1.5 g/dL, or cytogenetic response.ResultsThe rate of clinical benefit was higher with lenalidomide than with placebo (31.9% vs. 3.8%). The ratio of response (RBC-TI and clinical benefit) to risk (hematologic AEs) favored lenalidomide over placebo. Patients who underwent ≥ 1 lenalidomide dose reduction had a longer duration of treatment, received a higher cumulative dose, and were more likely to experience clinical benefit versus patients without dose reductions.ConclusionDespite the occurrence of hematologic AEs, the overall benefit-risk profile supported lenalidomide treatment. Appropriate management of hematologic AEs by dose reductions may help patients with myelodysplastic syndromes to remain on treatment and achieve clinical benefit.     

Autoimmune disorders in two patients with myelodysplastic syndrome and 5q deletion

Autoimmune diseases occurring concurrently with myelodysplastic syndrome (MDS) with deletion del(5q) including band q31 are very rare and have only been reported twice in the medical literature. We present two additional cases, one patient with del(5q) and trisomy 21 who suffered from rheumatoid arthritis and one patient with isolated del(5q) and autoimmune hemolytic anemia. Both patients had mild leukopenia and severe transfusion-dependent anemia. The rheumatoid arthritis was treated with antirheumatics without additional immunosuppressive medication. Autoimmune hemolytic anemia was controlled with long-term steroid administration. This patient developed additional trisomy 21, 2 years after the initial diagnosis of del(5q). Contrary to previous reports on autoimmune disorders in MDS mentioning improvements of hematological function in response to steroid administration, neither of our patients had a hematological improvement under corticosteroids.     

Current caesarean delivery rates and indications in a major public hospital in northern Greece

Background:   Over the past 25 years, there has been a sustained increase in caesarean section (CS) rates around the world. However, there is a paucity of data regarding the current CS rates and particularly the trends of CS indications in Greece.
Aim:   To assess the overall CS rates and indications in a major Greek teaching hospital over the last five years.
Methods:   All deliveries that took place in our Department between January of 2002 and December of 2006 were retrospectively analysed through manual medical chart review to record CS rates and indications.
Results:   During the study period, 4964 deliveries took place in our department; among them, 1831 were CS (36.9%). The overall caesarean delivery rate has remained stable during these five years (36.7% during 2002 vs 35.5% during 2006; P  = 0.633). The primary indications were previous caesarean delivery (30.9%), non-reassuring or pathological fetal heart rate trace by cardiotocography (12.3%) and dystocia (10.4%). The only indication whose rate significantly increased was previous caesarean delivery (+47.3%; P  = 0.002), whereas a significant decrease was found for non-reassuring or pathological fetal heart rate trace by cardiotocography (–39.1%; P  = 0.008).
Conclusions:   It is quite difficult to reduce the proportion of caesarean deliveries, particularly in a teaching hospital with a considerable number of high-risk pregnancies. The dominant role of previous caesarean delivery among CS indications stresses the importance of performing more vaginal birth after CS if we are to avoid the self-perpetuation of the CS epidemic.     

Evaluation of neutropenic fever: value of serum and plasma parameters in clinical practice

Treatment-related mortality due to infectious complications following potentially curable aggressive chemotherapy remains a major clinical problem. However, the diagnosis of neutropenic infections is difficult. Although it is common practice to institute empirical broad-spectrum antibiotics in neutropenic fever, liberal use of antibiotics may contribute to increasing resistance and superinfection such as systemic mycosis. Clinicians are searching for a highly specific and sensitive marker indicating early infection. Serum concentrations of several acute-phase proteins (C-reactive protein, serum amyloid A), proinflammatory cytokines (TNFalpha, IL-1, IFNgamma, IL-6, IL-8), soluble adhesion molecules (soluble E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1) and more recently procalcitonin have been investigated as to whether these may contribute to identifying infections as the cause of neutropenic fever. Unfortunately, at present, based on the small and inconsistent amount of data available from the literature one is tempted to conclude that the predictive values of all these parameters are too low to influence the clinically based initial treatment decisions in patients with neutropenic fever.     

Acute promyelocytic leukemia and pregnancy

In acute promyelocytic leukemia (APL), the use of all-trans-retinoic acid (ATRA) as a differentiating agent induces complete remission in a high percentage of patients. In pregnancy, however, this drug bears the risk of severe teratogenicity to the child. We report the case of a 23-yr-old woman at 21 weeks' gestation suffering from APL. She was treated with ATRA (45 mg/m2) for 40 d and two courses of standard chemotherapy. The mother achieved complete remission within 22 d of treatment. Fetal development was normal, and a healthy premature girl was born in the 35th week of pregnancy. In a review of the literature we have identified 14 cases of APL in pregnancy treated with ATRA alone or in combination with chemotherapy. ATRA has been used as early as in the 3rd week of gestation and in no case have malformations or other teratogenic effects occurred. Side-effects, however, ranged from fetal cardiac arrhythmias to induction of labour. Although known to exhibit severe teratogenic effects during the first trimester of pregnancy, ATRA seems to be reasonably safe during the second and third trimesters in the treatment of APL. However, careful obstetric follow-up is mandatory regarding fetal cardiac complications.     

Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group

Myelodysplastic syndromes (MDS) are a group of common bone marrow disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a substantial risk of progression to acute myeloid leukemia (AML). For many years, the main treatment option for MDS was best supportive care which alleviates symptoms, but has no effect on the natural course of the disease. Recently, demethylating agents have become available as a promising new treatment for patients with MDS. In two randomized clinical trials, the demethylating agent azacitidine has demonstrated a reduced risk of transformation to AML, improvement of peripheral blood values, an improved quality of life, and a definite survival advantage compared to conventional care regimens for patients with International Prognostic Scoring System score of intermediate-2 or high-risk MDS. This review aims to provide practical recommendations for the use of azacitidine and the management of its side effects in patients with MDS, assuring safe administration and best efficacy of treatment.     

Chronic myelomonocytic leukemia in the light of the WHO proposals

The WHO classification moved CMML to myeloproliferative/myelodysplastic disorders, and defined CMML I and CMML II according to medullary and peripheral blast count. To confirm these proposals, we analyzed 266 patients with CMML I and 73 patients with CMML II. Median survival time was 20 months for CMML I, and 15 months for CMML II (p<0.005). The cumulative risk of AML evolution differed between patient groups (p=0,001). No conclusive differences in clinical, morphologic, hematologic or cytogenetic parameters were found. These data support the WHO proposals for the classifi-cation of CMML.