FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.
Therapeutic results in elderly patients with acute promyelocytic leukemia (APL) have been generally reported as less effective than for younger patients. Patients 60 years or older with APL who were enrolled in 2 successive multicenter PETHEMA studies received induction therapy with all-trans retinoic acid (ATRA) and idarubicin, consolidation with 3 anthracycline monochemotherapy courses with or without ATRA, and maintenance with ATRA and low-dose chemotherapy. Eighty-seven of 104 patients achieved complete remission (84%). Eightysix proceeded to consolidation therapy (2 withdrew after the first and second courses). Deaths in remission occurred during consolidation and maintenance therapy in 3 and 4 patients, respectively. One patient showed molecular persistence after consolidation and 5 had a relapse. The 6-year cumulative incidence of relapse, leukemia-free survival, and disease-free survival were 8.5%, 91%, and 79%, respectively. A significantly higher incidence of low-risk patients found among the elderly, as compared to younger patients, may partially account for the low relapse rate observed. This study confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of protocols using ATRA and anthracycline monochemotherapy for induction and consolidation therapy in elderly patients. IntroductionThe outcome for patients with acute promyelocytic leukemia (APL) has dramatically improved with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. However, this improvement has been generally less impressive for the elderly than for younger patients. Due to the vulnerability to treatment toxicity in elderly patients, a reduction of chemotherapy intensity has been proposed for this age group. 1-4 However, whether the favorable impact of this reduction of chemotherapy on treatment-related mortality is counterbalanced by a lower antileukemic effect remains a matter of debate.Based on the excellent tolerance and high degree of compliance observed in the PETHEMA (Programa de Estudio y Tratamiento de las Hemopatías Malignas) studies using anthracycline/anthraquinone monochemotherapy for consolidation, 5,6 the dose and intensity of postremission therapy was not reduced for elderly patients. By contrast, consolidation therapy has been reinforced since 1999, regardless of age, for those patients with a higher risk.We report here the results from 104 consecutive patients with newly diagnosed APL who were 60 years or older and enrolled in 2 successive studies of the PETHEMA Group (LPA96 and LPA99). Patients, materials, and methodsPatients aged 60 years or older with de novo APL with demonstration of the t(15;17) or PML/RAR␣ rearrangements were included in the present study. Other eligibility criteria were: (1) normal hepatic and renal function, (2) no cardiac contraindications to anthracycline chemotherapy, and (3) Eastern Cooperative Oncology Group (ECOG) performance status less than 4. Informed consent was obtained from all patients.The induction regimen consisted ...
The optimal post remission therapy for HR-ALL patients (pts) is not well established. This multicenter randomized trial was addressed to compare three options of post remission therapy in adults with HR-ALL: intensive consolidation plus maintenance chemotherapy (CHT), ALLO or AUTO SCT. Inclusion criteria: one or more of the following: age 30–50 yr., WBC>25x109/L, t(9;22) or BCR/ABL, 11q23 or MLL and t(1;19). Treatment schedule: 5-drug (VCR, DNR, PDN, ASP, CPM) induction therapy over 5-weeks, followed by 3 1-wk cycles of early intensification CHT including HD-MTX, HD-ARAC and HD-ASP over 3 mo. Patients with an HLA-identical sibling were assigned to ALLO SCT and the remaining were randomized to AUTO SCT or to delayed intensification CHT (the same three cycles given in the post-remission period) followed by standard maintenance CHT (MP+MTX) up to 2-yr. in continuous complete remission (CR). Study period: 1993–2004, 254 pts included, 222 evaluable, 35 hospitals, 131 males, mean (SD) age 29(10) yr, WBC count 60(98) x109/L, early pre-B: 43 (19%), common+pre-B: 113 (51%), T: 66 (30%). Cytogenetics: 161 (73%) valid cases after central review, normal: 67 t(9;22): 37, 11q23: 6 cases, t(1;19): 2, other rearrangements: 49 cases. Response to therapy: CR 183 (82%). Slow response to therapy (>10% blasts in BM aspirate at day 14 of induction therapy) in 40% of cases. 84 pts were assigned to ALLO SCT, 50 randomized to AUTO SCT and 48 to CHT, 1 pt. removed from protocol after the end of induction. With a median follow-up of 70 mo.(range 24–133), medians for DFS and OS for the whole series were 17 and 23 mo., and 5-yr DFS and OS probabilities were 35±5% and 34±6% (37±6% and 35±6% after removing Ph+ ALL pts from analysis). Groups of ALLO, AUTO and CHT were comparable for the main clinicobiologic characteristics and the rate of response to therapy. Intention-to-treat analysis showed no differences in DFS and in OS for donor vs. no donor comparison as well as for comparison of AUTO vs. CHT. This lack of differences persisted after removing Ph+ ALL pts from the analysis. The same results were observed when the analysis was performed on the basis of effectively treated pts (ALLO SCT performed in 70%, AUTO SCT in 62% and CHT in 73% of the pts). By multivariate analyses, age>30 yr. was associated with death in induction, slow response to induction therapy and Ph+ ALL were associated with a lower CR, and these three variables had a negative influence on DFS and on OS probabilities. No differences in outcome were found in pts assigned to ALLO SCT or randomized to AUTO SCT or CHT as post-remission therapy in HR-ALL. DFS from ALLO or AUTO SCT or from intensification therapy was also identical in effectively treated patients. Adults with Ph+ ALL or slow response to induction therapy have been identified as a very-high-risk ALL subgroup for whom specific or experimental therapies are justified.
The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.
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