Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib.

In this study, we report the case of a Philadelphia (Ph) positive chronic myelogenous leukemia (CML) patient with the presence of p190 and p210 BCR-ABL1 mRNA fusion transcripts derived from e1a2 and b3a2 BCR-ABL1 genomic rearrangements, respectively. The presence of e1a2 BCR-ABL1 genomic rearrangement was seen in 2 different clones, one with the rearrangement and another one with the rearrangement and deletion of the BCR gene of the non-rearranged chromosome 22. After treatment with imatinib, the p210 transcript could not be detected, whereas p190 was still present 6 months after initiation of imatinib therapy and progression to blast phase. The absence of p210 transcript post treatment indicates that the clone with b3a2 responded to imatinib and that the observed resistance was associated to cells harboring the e1a2 genomic rearrangement. Despite resistance of this patient to imatinib, no evidence of mutations in the kinase domain of ABL1 was found. Loss of normal BCR in one cell clone may contribute to the resistance to imatinib due to the lack of BCR mediated inhibition of BCR-ABL1.

All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia.

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%). Eighty-six 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.

[Incidence of bacteremia among histologic groups of hematologic malignancies]. / Incidencia de bacteriemia en grupos histológicos de neoplasias hematológicas.

INTRODUCTION: Subgroups having dissimilar prognoses are being identified among cancer patients with infection. Previous studies have suggested that these differences may be related to the histologic diagnosis, but this issue has not as yet been demonstrated. METHODS: We reviewed the medical records of all patients admitted with acute leukemia (AL) or lymphoma (ML) from 1988 to 1998. Incidence of bacteremia was calculated for the following subgroups: acute lymphocytic leukemia (ALL), acute myelocytic leukemia (AML), AML following refractory anaemia with excess blasts (AML-RAEB), high-grade ML (HGML), intermediate-grade ML (IGML), low-grade ML (LGML) and indeterminate ML (IML). Kaplan-Meier curves of time to the first positive blood culture were constructed and compared by means of log-rank test. RESULTS: In the period covered there were 244 new diagnoses of AL or ML: 62 AML, 32 ALL, 20 AML-RAEB, 78 HGML, 7 IGML, 37 LGML and 6 IML. At the end of the study period, 44 patients were alive, 147 were known to have died at a certain date and 53 had been formally lost to follow-up (most of them, transferred for hospice care). Among 684 blood cultures, there were 51 contaminations and 155 significant isolates. Among the latter, gram-positive bacteria were isolated in 74 and gram-negative bacteria in 47; in 27 cases more than 1 bacterial species were recovered. Fungi were isolated in 7 cases. The incidence of bacteremia expressed as cases per 1000 patient-days was 5.80 for AML, 5.03 for AML-RAEB, 1.56 for ALL, 0.21 for HGML and 0.40 for the remaining ML. Time to the first positive blood culture was significantly shorter for AML than for any other group, and was shorted for ALL and AML-RAEB than for ML. CONCLUSION: Differences in the incidence of bacteremia were observed among histologically-defined groups of unselected patients with hematologic malignancies.