Results with Randomized BFM Adopted Studies for ALL Therapy in Childhood in East German Countries

Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclin‐dependent kinases (cdk2, cdk4) and tumor‐suppressor genes (pRb, p16INK4A), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse‐free‐intervals or the frequency of recurrence in patients. Children with cdk4‐positive ALL had a lower probability of remaining in first continuous remission than children with cdk4‐negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance. Int. J. Cancer 74:508–512, 1997. © 1997 Wiley‐Liss, Inc.

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“…Patients with an initial presentation of ALL were treated according to 2 modified BFM protocols, ALL-VII/81 and ALL-VIII/87 (Zintl et al, 1993).…”

Section: Treatmentmentioning

confidence: 99%

Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRb, p16INK4A) in childhood acute lymphoblastic leukemia

et al. 1997

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“…(Zintl et al, 1993) and ALL-BFM-90 (Riehm et al, 1992)]. These treatment protocols consist of induction therapy with prednisone, vincristine, daunorubicin and L-asparaginase followed by consolidation therapy with cyclophosphamide, cytarabine, 6-mercaptopurine and intrathecal methotrexate (MTX).…”

mentioning

confidence: 99%

P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia

Sauerbrey

Zintl²,

Volm³

1994

Br J Cancer

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Summary Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transferase (GST-it) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-i was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21 %), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-I 70-negative tumours (P < 0.05J. However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-i was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-i was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.The results of chemotherapy on childhood acute lymphoblastic leukaemia (ALL) have been markedly improved during the past decade (Riehm et al., 1992). The remission rate of patients treated with chemotherapy is more than 95%, and the long-term disease-free survival rate about 75%. In spite of these excellent results, 25% of the patients will experience a relapse with a poor prognosis. The search for risk factors to define patients at high risk of relapse who need a different or more aggressive therapy is thus a current problem.

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Apoptotic index, Fas and bcl-2 in initial and relapsed childhood acute lymphoblastic leukaemia

et al. 1997

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Seventy-two samples with initial and 23 samples with relapsed childhood acute lymphoblastic leukaemia (ALL) were investigated for apoptotic index (AI) and for Fas expression. AI was determined by DNA-fragmentation using deoxynucleotidyl terminal transferase and Fas expression by immunocytochemistry. bcl-2 mRNA expression was measured in 50 initial and 20 relapsed ALL. The patients were discriminated in groups with low and high AI, Fas-protein expression and bcl-2mRNA expression by the mean value. AI was higher in relapsed than in initial ALL. The mean survival was significantly higher in patients with low AI (p= 0.034). This was also true for the relapse-free interval, however, this result was borderline significant (p= 0.064). AI was directly correlated with expression of Fas and inversely correlated with bcl-2 mRNA expression. These results suggest that Fas and - with limitations - bcl-2 may influence the apoptotic process in childhood ALL and that enhanced apoptotic activity predicts poor prognosis.

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Results with Randomized BFM Adopted Studies for ALL Therapy in Childhood in East German Countries

Cited by 3 publications

References 3 publications

Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRb, p16INK4A) in childhood acute lymphoblastic leukemia

Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRb, p16INK4A) in childhood acute lymphoblastic leukemia

P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia

Apoptotic index, Fas and bcl-2 in initial and relapsed childhood acute lymphoblastic leukaemia

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