The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients.

IntroductIon L-asparaginase is an enzyme of the hydrolase class that catalyzes the degradation of L-asparagine-an amino acid (amide of 2-aminosuccinic acid), to aspartic acid and ammonia. This enzyme is present in numerous bacteria, plants and animals. However, it has not been found in humans. The presence of L-asparagine is essential for a normal course of the cell cycle. In most human cells the deficit of the endogenous asparagine may be compensated by alternative synthesis from aspartic and glutamine acid involving the asparagine synthase. This enzyme is absent in certain neoplasmatic cells, particularly in lymphoblasts, thus the depletion of L-asparagine from the plasma leads to DNA, RNA and protein synthesis inhibition and in consequence to blast cell apoptosis. L-asparaginase demonstrates relative substrate specificity and

Outcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new salvage regimen (FLAM) consisting of sequential fludarabine, cytarabine, and mitoxantrone. Fifty patients were included with primary (n = 13) or secondary (n = 5) refractoriness, early (<12 months) first relapse (n = 15), first relapse after hematopoietic cell transplantation (HCT) regardless CR duration (n = 13), and second or subsequent relapse (n = 4). Median age was 31(18-60) years, 28% of patients were bcr/abl-positive. CR rate equaled 50% and was significantly higher for patients in whom FLAM was administered as a second-line therapy compared to those more heavily pre-treated (66 vs 13%, p = 0.02). Seventeen patients had leukemia regrowth after initial cytoreduction, whereas, eight patients died in aplasia. The incidence of early death was higher in patients aged > or =40 years compared to the younger subgroup (33 vs 8%, p=0.03). Septic infections were the most frequent severe complication. At 3 years, the probability of disease-free survival for patients who achieved CR equaled 16%. Seven patients underwent allogeneic HCT. FLAM regimen is feasible for relapsed and refractory adults with ALL and could be recommended in particular for younger patients as a second-line treatment. However, as the remission duration is short, allogeneic HCT (alloHCT) should be considered as soon as possible.

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

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