| Acute promyelocytic leukemia (APL) is the most curable subtype ofAML in adults now. However, despite this progress, treatment failure stilloccurs in patients who have gained long-term remission because of morefrequently CNS relapse which has been increasingly reported recently. Theinvolvement of CNS in APL is becoming one of important factors thatthreaten long-term survival. To better investigate and reveal these studies andthe prognostic factors influencing relapse and highlight the importance ofitentifying the APL patients at high risk of relapse, direct the risk-adaptedpotential prognostic strategy, ultimately improve chances of prolongedremission, here we present a retrospective study. Patients and Methods: A total of 50 APL patients performed in ourhospital between January, 1996 and March, 2006 have been registered for theretrospective study of clinical features, biologic characteristics and treatmentregimen evaluable analyses including two groups: Group A, 14 patients withCNS relpse;Group B, 36 patients without CNS relapse who have experienceda history longer than 36 months. Results: 1.There was no significant difference between the two groupswith respect to gender (P>0.05). Difference in age distribution was notstatistically significant. Difference in clinical performance at presentation wasnot statistically significant, either (P>0.05). 2. With respect to peripheral cellcounts, leukocyte count (WBC) was found to be statistically significant(P<0.05). After selecting WBC count with the cut-off point of 10×109/L,15×109/L and 50×109/L, the discriminating cut-off value was shown to be50×109/L between Group A and B (33.33%versus3.13% respectively, P<0.05).The HGB level and PLT count did not differ from each other significantly(P>0.05). 3.Minor difference in the percentage of bone-marrowpromyolocytes was shown between Group A and B, as well as that ofperipheral promyolocytes (P>0.05). 4. There was no difference betweenGroup A and B with respect to the chromosomal abnormalities including thetypical t (15;17) translocation and additional karyotypic ones (P>0.05). Thelong and short PML-RAR fusion transcripts were examined and eachproportion in Group A and B showed as follows: 83.33% and 16.67%, 93.10%and 6.9%, respectively. No statistically significant association was found(P>0.05). 5. Due to immunophenotypic assays were carried out for one patientin Group B only, no statistical analysis was performed. 6. All patients' cardial,hepatic and renal function were normal. Difference in the LDH level was notsignificant between the 2 groups (P>0.05). 7. The proportion patients whounderwent neither systemic nor intrathecal prophylaxis chemotherapy ofGroup A was 50%, whereas that of Group B was 38.89%. But the differencewas not statistically significant with respect to prophylactic administration,containing systemic or intrathecal chemotherapy either concomitantly or alone,the same as frequency of intrathecal chemotherapy. The analysis did notreveal any significant effect of administration of ATRA and occurence of RAS(P>0.05). 8. Hematological CR were achieved in all the patients. The mediancycle to achieve hematological CR of Group A were longer than that of GroupB (1.14±0.36 versus 1.00±0.00 respectively, P<0.05). However, days toachieve hematological CR did not differ significantly (1.63±0.96m versus1.64±0.51m, respectively, P>0.05) No statistically significant difference ofmolecular CR was found, evaluation of which was based on conversion fromRT-PCR-positive to RT-PCR-negative status tested for PML-RAR hybrid(P>0.05). 9. Incidence of hematologic relapse rate of Group A (35.71%) washigher than that of Group B (22.22%), interval from the date of APL diagnosisto that of hematologic relapse of Group A was shorter than that of Group B,aswell as CR maintenance (26.56±7.51m versus31.06±14.99 m, 24.66±8.07 mversus 29.38±15.00 m, respectively). But difference was not found to bestatistically significant (P>0.05). Molecular relapse monitoring was assessed byRT-PCR, but there was not adequate on-study data available. None of patientsexperienced extramedullary (EM) relapse involving other sites except CNS.Conclusion:1.Initial peripheral hyperleucocytosis is identified as anadverse prognostic factor for CNS relapse. CNS relapse in APL occurs morefrequently in patients with increased WBC count greater than 50×109/L atdiagnosis.2.Prolonged cycle (>1) to achieve hematological CR is a riskpredictor of CNS relapse.3. PML-RAR (S+)isoform and younger age may becorrelated to high WBC count. Occurence of PML-RAR (S+) isoform maybe associated with an increased risk of CNS relapse and should be consideredas an unfavorable factor. It is suggested risk-adapted strategies focusing onsuch patients.4.CNS prophylaxis by systemic or intrathecal chemotherapymay produce a possible effect on reducing occurrence of CNS relapse, andparticularly high-risk patients may benefit from it. 5. The confoundingmultiple factors influcing CNS relapse are complex interacted, specifictreatment such as prospective strategy and individualized regimen should beperformed clinically as early as possible.
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