Susanna Fenu

Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7

We reviewed the clinical features, treatment, and outcome of 100 children with myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML) associated with complete monosomy 7 (−7) or deletion of the long arm of chromosome 7 (7q−). Patients with therapy-induced disease were excluded. The morphologic diagnoses according to modified FAB criteria were: MDS in 72 (refractory anemia (RA) in 11, RA with excess of blasts (RAEB) in eight, RAEB in transformation (RAEB-T) in 10, JMML in 43), and AML in 28. The median age at presentation was 2.8 years (range 2 months to 15 years), being lowest in JMML (1.1 year). Loss of chromosome 7 as the sole cytogenetic abnormality was observed in 75% of those with MDS compared with 32% of those with AML. Predisposing conditions (including familial MDS/AML) were found in 20%. Three-year survival was 82% in RA, 63% in RAEB, 45% in JMML, 34% in AML, and 8% in RAEB-T. Children with −7 alone had a superior survival than those with other cytogenetic abnormalities: this was solely due to a better survival in MDS (3-year survival 56 vs 24%). The reverse was found in AML (3-year survival 13% in −7 alone vs 44% in other cytogenetic groups). Stable disease for several years was documented in more than half the patients with RA or RAEB. Patients with RA, RAEB or JMML treated with bone marrow transplantation (BMT) without prior chemotherapy had a 3-year survival of 73%. The morphologic diagnosis was the strongest prognostic factor. Only patients with a diagnosis of JMML fitted what has previously been referred to as the monosomy 7 syndrome. Our data give no support to the concept of monosomy 7 as a distinct syndrome.

Treatment of acute myeloid leukaemia patients with recombinant interleukin 2: a pilot study

Summary. Twelve patients with acute myeloid leukaemia (AML) with evidence of resistant disease were treated with recombinant interleukin 2 (rIL2) given intravenously by continuous infusion. No objective response to rIL2 alone was documented in the seven patients with advanced disease (20–90%, resistant blasts in the marrow), except for a partial response to rIL2 plus chemotherapy in one. Of the five patients with limited disease (8–15% marrow blasts), three obtained a complete disappearance of the blasts following two to four 5 d courses of rIL2 alone. One patient persists in fourth complete remission (CR) 30 months later, another obtained a third CR for 4 months, and the last remained in third CR for 9 months before relapsing. This latter patient achieved a fourth CR with low‐dose cytarabine. The remissions have been maintained with low‐dose monthly courses of rIL2 given on an out‐patient basis. Two AML did not respond to rIL2 alone; one, however, obtained a fourth CR with chemotherapy and rIL2. Administration of rIL2 was accompanied by organomegaly and leucocytosis, with a frequent lymphocytosis and increase in eosinophils and large granular lymphocytes, both in the blood and in the marrow. Side effects, though often severe, were controllable using a daily dose escalating protocol and never required intensive care treatment. The results of this pilot study indicate that treatment of AML patients with rIL2 is feasible and may result in the disappearance of chemotherapy‐resistant blasts in patients with limited but detectable disease. Further controlled trials in AML in CR appear warranted.

The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML)

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 × 109/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 × 109/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.

Real-life use of erythropoiesis-stimulating agents in myelodysplastic syndromes: a “Gruppo Romano Mielodisplasie (GROM)” multicenter study

The Gruppo Romano Mielodisplasie (GROM) conducted a retrospective study in 543 patients with myelodysplastic syndromes (MDS) to evaluate the safety and efficacy of erythropoiesis-stimulating agents (ESAs) in “real-life” clinical practice. The 40.000-UI/week erythropoietin (EPO)-alpha and 30.000-UI/week EPO-beta starting dose were defined “standard,” and 80,000xa0UI/week EPO-alpha and 60.000xa0UI/week EPO-beta were defined “high.” Response was defined according to International Working Group (IWG) 2006 criteria. At ESA’s start, median age was 74.2xa0years (interquartile range (IR) 67.8–79.5) and median hemoglobin was 8.9xa0g/dl (IR 8.2–9.6). Median time from diagnosis to ESAs start was 3.8xa0months (IR 0.8–13.2). ESA starting dose was “standard” in 361 patients (66.5xa0%) and “high” in 182 patients (33.5xa0%). Erythroid response was observed in 82/185 (44.3xa0%) transfusion dependent (TD) patients as compared with 226/329 (68.6xa0%) transfusion independent (TI) ones (pu2009<u20090.001). At multivariate analysis, in TD patients, only endogenous EPO levels <50xa0mU/l were significant (pu2009=u20090.046), whereas in TI patients, high-dose ESAs (pu2009<u20090.001), abnormal creatinine levels (0.009), and endogenous EPO levels <50xa0mU/l (pu2009=u20090.014) were predictors of response. Responders showed a higher 5-year overall survival (OS) (57.8 vs. 32.2xa0%, pu2009<u20090.001) and leukemia-free survival (76.0 vs. 49.8xa0%, pu2009<u20090.001). At multivariable analysis for OS, response to ESA, low International Prognostic Scoring System (IPSS), no transfusion need, and female sex showed an independent favorable prognostic role. Our results confirm that treatment with ESAs is effective in a real-life MDS setting, particularly at high dose and in TI patients. Prospective studies are needed to define the optimal starting dose.