Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR-ABL--positive acute lymphoblastic leukemia-retrospective analysis of Polish Adult Leukemia Group (PALG).

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.

The treatment of acute myeloid leukemia with mitoxantrone, etoposide and low-dose cytarabine in elderly patients - a report of Polish Acute Leukemia Group (PALG) phase II study.

The common dilemma in the treatment of elderly patients with acute myeloid leukemia (AML) is whether to use intensive myelosuppresive therapy with higher risk of treatment related mortality (TRM), but a chance for complete remission (CR), or to treat less intensively in order to prolong survival time with a better quality of life. The aim of this prospective, phase II study was to assess the efficacy and toxicity of low dose combination induction treatment consisted of cytarabine at a dose of 10 mg/m2 every 12 h s.c. for 7 days, VP-16 at a dose of 100 mg/day p.o. for 7 days and mitoxantrone at a dose of 6 mg/m2 i.v daily on days 1-3. Two induction courses were planned. In the group of 44 patients 12 (27%) achieved CR, 4 (9%) patients were in PR and there were 9 (20%) early deaths (ED). Age, performance status, preceding myelodysplastic syndrome, karyotype, WBC and % of blasts in bone marrow were not significant prognostic factors for CR probability. The following initial factors appeared to be related to a shorter duration of survival time from the start of treatment: age >70 (p<0.03), poor performance status (p<0.03), and % of BM blasts 50 (p<0.05). We conclude that, despite promising results in the pilot study the efficacy of this induction treatment is not better than the efficacy of other regimens. The hematological toxicity of this treatment seems to be comparable with "3+7" regimen.

2-Chlorodeoxyadenosine (cladribine)-related eosinophilia in patients with lymphoproliferative diseases.

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.

Activity of 2-chlorodeoxyadenosine (Cladribine) in 2-hour intravenous infusion in 94 previously treated patients with low grade non-Hodgkin's lymphoma.

The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine (2-CdA) administered in 2-hour intravenous infusions in previously treated patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median 3), repeated usually at monthly intervals. All patients were refractory to or relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In 12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade 4 neutropenia was observed in 12 (12.8%) and infections complicated the course of treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3 patients. The results of our study show that 2-CdA given in 2-hour infusions is an effective agent in advanced, heavily pretreated patients with LGNHL.

Interferon production by peripheral blood leukocytes of patients with acute myeloid leukemia.

The ability of peripheral blood leukocytes (PBL) of 13 selected patients with acute myeloid leukemia (AML), and of 10 healthy subjects to produce interferon (IFN) spontaneously and after in vitro induction was tested. Spontaneous IFN production was detected in supernatants of PBL cultures of healthy subjects but was not present in cultures of leukemic cells (leukocytes density 1 x 10(6) ml). After induction with Newcastle disease virus (NDV) PBL cultures from 5 patients with AML exhibited a low IFN response, while in others IFN titers were similar to controls. The IFN titers induced with lipopolysaccharide (LPS) were lower in leukemic cells than those detected in control cells. The absence or low IFN levels after induction with phytohemagglutinin (PHA) correlated with very small numbers of normal lymphocytes in blood of leukemic patients.

[Clinical and immunologic characteristics of CD 34 positive acute myeloid leukemia]. / Charakterystyka kliniczna i immunologiczna ostrej bialaczki szpikowej CD 34 dodatniej.

Expression of antigen CD 34+ on acute myeloid leukemia is admittedly regarded as a negative prognostic factor, however some authors deny it. The aim of our studies was clinical, morphological and immunological analysis of AML CD 34+. In the group of 39 patients with de novo AML there was 46% of AML CD 34+ (18 cases--14 women and 4 men aged 18 to 80 years--mean 52.5). The diagnosis was made according to FAB criteria and immunophenotype estimation by immunocytochemical method APAAP. The following types of AML were found: MO-4 cases, M1-1, M2-4, M4-8, M5-1. Analysis of clinical features of AML CD 34+ did not show any characteristic features either in peripheral blood smear, or bone marrow smear. Most patients were treated according to the EPR+Ara-C scheme, with addition of VP-16 in M4 types, one patient--IDA+VP-16 + Ara-C, three elderly patients were treated with low doses of Ara-c, one patient refused cytostatic treatment. Three patients achieved complete remission (17.6%), three achieved partial remission (17.6%), four died during the phase of aplasia and seven others (41.2%) were completely resistant for chemotherapy. These results confirm association between CD34 expression and drug resistance.

[Spontaneous and induced production of tumor necrosis factor (TNF alpha) by peripheral blood leukocytes in patients with acute leukemia type M 4 and M5 according to FAB]. / Spontaniczne i indukowane wytwarzanie czynnika martwicy nowotworów (TNF alpha) przez leukocyty krwi obwodowej chorych na ostra bialaczke typu M4 i M5 wg FAB.

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological activity. We have undertaken the present study to evaluate a possible ability of peripheral blood cells of healthy subjects and patients with acute monocytic leukemia to produce TNF alpha. We studied 17 leukemia patients and 8 control subjects. Spontaneous production of TNF alpha induced by LPS and Newcastle disease virus (NDV) were determined in blood cell cultures. Leukemic cells released markedly higher level of TNF alpha than control cells cultured in vitro in contrast to control cells producing TNF spontaneously. It seems that leukemic cells can produce TNF in response to very small amount of LPS; however, we cannot exclude that spontaneous TNF may be involved in autocrine regulation of proliferation and differentiation of bone marrow monocyte precursors.