[Monitoring of minimal residual disease in patients with acute promyelocytic leukemia].

AIM: To study efficacy of different programs of maintenance therapy, to create the program of differential therapy of minimal residual disease (MRD) and molecular recurrences at all stages of acute promyelocytic leukemia (APL) basing on the results of monitoring. MATERIAL AND METHODS: A total of 76 APL patients entered the trial. They received therapy by the protocols APL-97/98, APL-01, AIDA, 5D. Expression of chymeric oncogen PML/RARa in the disease onset was estimated by bone marrow and/or peripheral blood examination with RT-PCR. The study of chymeric oncogen PML/RARa was made once in two months. RESULTS: The program of differential therapy of APL is proposed on the basis of molecular-biological monitoring of expression of chymeric oncogen PML/RARa. The results of molecular monitoring of MRD correlated with development of molecular and hematological recurrences. Therapeutic policy is determined after diagnosis of molecular recurrence. Further therapy of APL is determined which allows a rise in overall and recurrence-free survival of the patients. CONCLUSION: The efficacy of maintenance therapy only with cytostatic drugs or their combination with ATRA is similar. The response to biological therapy with ATRA plus interferon-alpha is not sufficient. Molecular recurrences--probable or documented--are detected in maintenance therapy 2 months earlier, on the average, than hematological ones. Changes in the treatment policy in registration of molecular recurrence significantly diminish probability of hematological recurrence (from 36 to 0%, p = 0.001.

[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias]. / Predvaritel'nye rezul'taty mnogotsentrovogo randomizirovannogo issledovaniia po lecheniiu ostrykh promielotsitarnykh leikozov.

AIM: To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial. MATERIAL AND METHODS: The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant. RESULTS: 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03). CONCLUSION: The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.

[Liposomal daunorubicin and interferon-alfa in combination with all-retinoic acid--a new regime for the treatment of acute promyelocytic leukemia]. / Liposomal'nyi daunorubitsin i interfron-al'fa v sochetanii s polnost'iu transretinoevoi kislotoi--novaia programma lecheniia ostrykh promielotsitarnykh leikozov.

AIM: To define duration and schemes of maintenance therapy, to evaluate cytarabine demand while treatment of acute promyelocytic leukemia (APL) with an original program 5D + Ifa + AT RA. MATERIAL AND METHODS: The above treatment was conducted in 7 patients with APL (1 male, 6 females, 18-45 years, leukocytes 1.2-15.0 x 10(9)/l). RESULTS: Induction by 5D program was performed in 5 patients. A complete remission was achieved in 4 of them, molecular--in 3. One woman died. 5D consolidation was performed in 6 patients. After the first course of consolidation all the patients achieved molecular remission. Maintenance of remission with Ifa + ATRA was made in 5 patients. In one female the remission came to the end. Mean time of the follow-up was 18 months. The remission lasted 5-36 months. Monitoring of molecular remission has not found marker PML/RARa. CONCLUSION: Daunozom monotherapy leads to a complete remission after the first course in most of the patients. In the majority of them it was molecular. Maintenance with If + ATRA for 2 years maintains molecular remission for 5-36 months.