Treatment of chronic myeloid leukemia in the blastic phase with fludarabine, cytosine arabinoside and G‐CSF (FLAG)

Abstract

The present study was undertaken to evaluate the efficacy of the association of fludarabine plus Ara-C and G-CSF (FLAG) in the treatment of 15 patients with chronic myeloid leukemia in the blastic phase (CML-BP). Patients achieving a partial remission (PR) after the first course received a second FLAG. Complete remission (CR) was consolidated with another FLAG regimen. Patients were then submitted to an individualized program of treatment depending on age and suitable donors. Overall seven patients achieved CR (46.7%), three (20%) showed a primary resistant disease, while three (20%) died during remission induction therapy. Five of them received a consolidation therapy; in two cases further treatment was not performed because of severe toxicity. Median overall survival and disease-free survival were of 7.5 and 4.5 months, respectively. FLAG proved to be effective in achieving a high CR rate in patients with CML-BP. Median overall survival and disease-free survival were not significantly improved compared to previous studies. Nevertheless, the treatment was well tolerated even in a group of heavily pretreated patients, allowing further transplantation opportunities in younger patients.

Single-agent therapy with oral mercaptopurine for nonlymphoid blast crisis of chronic myeloid leukemia

“…No significant difference was found in the survival of both treatment groups, with the median survival registered in the two groups being similar to that reported in most BC series [8,9,13,14,15,16,17,18,19,20,21,22,23,24]. However, when considering the time spent in hospital as a meaningful indicator of the patients' quality of life, patients treated with i.v.…”

“…Such a low response rate, as compared to the results reported in other studies, may be related to the exclusion of lymphoid BC, to the use of stringent response criteria in our series, and to the fact that the chemotherapy doses of most of the regimens employed in the present series would not be currently regarded as "intensive," although these regimens usually resulted in a marked and long-lasting myelosuppression. In addition, it must also be considered that in BC increasing dose intensity has failed to improve patients' survival [22,23,24]. As far as therapy with oral 6-MP is concerned, such a conservative approach allowed an adequate control of the WBC counts in most cases but, as expected, did not lead to the achievement of major responses.…”

“…Following the strategy successfully employed in acute leukemia, escalation of treatment dose intensity has been attempted to improve such poor results. Most of the intensive chemotherapy regimens used have been based on the use of intravenous AraC, alone [14] or in combination with other agents, including m-AMSA [19], anthracyclines [13,16,18,22], carboplatin [20], fludarabine [24], or VP-16 [20]. Moreover, post-remission intensification therapy with hematopoietic stem cell transplantation has also been performed in some cases [25,26,27].…”

“…Although different therapeutic strategies have been investigated to overcome such treatment refractoriness, comparison of the results is difficult due to the heterogeneity of the published studies [7,8,9,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27], particularly in the criteria used for BC diagnosis, patient selection, and therapeutic response. Management of nonlymphoid BC with single agent oral chemotherapy, such as hydroxyurea or decytabine, is associated with low response rates, ranging from 0 to 20%, and short survival [7,8,23].…”

“…In these latter cases, different chemotherapy regimens have been attempted, ranging from single agent oral chemotherapy to acute leukemia-like regimens [13,14,15,16,17,18,19,20,21,22,23,24] and even stem cell autologous transplantation as post-remission intensification [25,26,27]. However, complete remission rates remain consistently low, and the median survival of these patients ranges from 3 to 5 months [17,18,19,20,21,22,23,24,25,26,27]. Since limited data are available in the medical literature on the results achieved by a conservative treatment approach to nonlymphoid BC with oral chemotherapy, it is uncertain whether intensive chemotherapy provides any advantage, especially when considering the toxicity associated with intensive regimens, the low response rate, and the short duration of the response.…”