Flang (Fludarabine + Cytosine Arabinoside + Novantrone + G-CSF) Induces Partial Remission in Lymphoid Blast Transformation of Ph⁺ Chronic Myelogenous Leukaemia

Abstract

The adenine nucleoside analogue, fludarabine phosphate, in combination with cytosine-arabinoside (Ara-C) and granulocyte-colony stimulating factor (G-CSF) (the so called FLAG regimen) has recently been shown to be effective in the treatment of poor-prognosis acute non-lymphoid leukaemia. We used this combination plus novantrone (FLANG regimen) in a case of Ph¹+ chronic myeloid leukaemia (CML) unresponsive to interferon alpha that had progressed to an acute phase, after 3 months of treatment with 6-mercaptopurine and hydroxyurea. The patient was treated with two courses of fludarabine 30 mg/m² (days 1–5) + Ara-C 2 g/m² (days 1–5) + novantrone 5 mg/m² (days 1–3) and G-CSF from day 0 to neutrophil recovery. After the first cycle of chemotherapy, bone marrow blasts decreased from 100% to less than 5% (clinical complete remission), with a progressive clearance of Ph¹+ metaphases (from 100% to 12%). At the end of the second course, a progressive increase of blasts was observed again and karyotypic detection of Ph⁺ cells was also documented (from 12% to 42.9%). During this partial remission, the patient underwent an allogeneic bone marrow transplantation from an HLA matched identical brother. At the time of this report, he is still alive and well and in complete karyotypic remission. This partial therapeutic success was compared with the result obtained in another previously reported CML case: differences in the therapeutic efficacy of protocols employing fludarabine nucleosides and the type of blastic cells involved are discussed.

Key Words:

• chronic myelogenous leukaemia
• lymphoid blastic phase
• fludarabine
• nucleosides
• BCR-ABL
• mRNA