High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia

Abstract

Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph þ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.

Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy

“…Two recent frontiers in leukemia research are the emergence of imatinib-resistant CMLs [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] and the discovery of mutations at the Jak2 kinase in certain myeloproliferative diseases. These topic areas document the importance of genetic approaches in leukemia and abnormal hematopoiesis research as they were discovered upon identification of the genetic mutations responsible for the hematopoietic neoplasia.…”

Nilotinib restores long-term full-donor chimerism in Ph-positive acute lymphoblastic leukemia relapsed after allogeneic transplantation

“…In addition, she received imatinib 400 mg BID over 28 days according to a modified regimen consisting of high-dose imatinib combined with VCR and dexamethasone. 9 The patient achieved hematologic remission with persistence of M-BCR positivity and a mixed chimerism. Sequencing analysis of reverse transcriptase-PCR product found no BCR-ABL mutations.…”

Acute Lymphoblastic Leukemia (ALL) Philadelphia Positive (Ph1) (Incidence Classifications, Prognostic Factor in ALL Principles of ALL Therapy)

“…Patients older than 55 experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients. [23] …”