FLT3 Inhibitors for Treating Acute Myeloid Leukemia.

FLT3 (Fms-like tyrosine kinase 3) inhibitors are tyrosine kinase inhibitors. The first-generation FLT3 inhibitors were developed several years ago and include midostaurin, lestaurtinib, sunitinib, and sorafenib. They are relatively nonspecific for FLT3, with other potential targets that include platelet-derived growth factor receptor, vascular endothelial growth factor receptor, KIT, and Janus kinase 2. The second-generation inhibitors, including quizartinib, crenolanib, PLX3397, and ASP2215, are more potent and selective than the first-generation inhibitors. The greater potency and selectivity promises greater efficacy in FLT3-mutated acute myelogenous leukemia (AML) (particularly in patients with a greater allele burden) and less toxicity. A number of receptor tyrosine kinase inhibitors are being studied across virtually all disease settings, including frontline, relapsed and refractory, and maintenance, mainly in patients with FLT3-mutated AML. The future of FLT3 inhibitors in the treatment of AML, in combination with chemotherapy or stem cell transplant, appears bright. The present report reviews the current data on FLT3 inhibitors.

Leukemia during pregnancy: long term follow up of 32 cases from a single institution.

BACKGROUND AND OBJECTIVES: There is limited information regarding the outcome of patients treated for leukemia during pregnancy. This study was performed on all cases of leukemia during pregnancy identified in our institution leukemia database. PATIENTS AND METHODS: It is a retrospective study from our existing database. Thirty two cases were identified among the cohort of patients treated for acute and chronic leukemia between January 1991 and July 2003. RESULTS: Among the acute leukemia patients (n=21), 10 patients (47.6%) received chemotherapy during pregnancy, seven had live birth and three had spontaneous abortion. No teratogenicity or congenital malformations or postnatal complication were reported. The remaining 11 (52.4%) were not given chemotherapy while pregnant; three patients presented after 34 weeks of gestation ending in normal live births and then received chemotherapy and eight patients had abortion before starting chemotherapy. Among the chronic myeloid leukemia (CML) patients (n=11), nine patients received hydroxyurea, one patient received alfa-interferon and one patient was treated with leukapheresis. Eight patients had normal live births and three patients had abortion. Out of the 32 patients, 18 patients (56.2%) subsequently underwent HLA matched sibling allogeneic stem cell transplantation, seven for acute myeloid leukemia (AML), two for acute lymphocytic leukemia (ALL) and nine for CML. After a median follow up of 16 years, five patients (15.6%) are alive in remission (one from chemotherapy group and four from SCT group). CONCLUSIONS: Our report lends credence to the safety and feasibility of administering anti-leukemic therapy in acute and chronic leukemias during pregnancy although acute leukemia patients had possibly a poor long term outcome compared to non-pregnant patients.

Rituximab in immune thrombocytopenia: transient responses, low rate of sustained remissions and poor response to further therapy in refractory patients.

Management of patients with immune thrombocytopenia (ITP) refractory to standard treatment is difficult. Recent studies show that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of ITP. We retrospectively studied 24 patients who received 29 rituximab treatments for relapsed or refractory ITP. Patients had received a median of 3 treatment regimens before (range 1-8) and 11 patients had prior splenectomy. Responses were achieved in 19 of 29 (66%) treatments. The median time to response was 3 weeks (range 1-20) from the start of therapy and median duration of response was 13 weeks (range 1 week-55 months). Responses were mostly short lived and after a median follow-up of 22 months (range 2-70), 10 (34%) responses were sustained after 6 months, 7 (24%) responses sustained after 1 year and only 5 patients continued to have a response at last visit after 8, 10, 24, 30 and 54 months of follow-up. Previous splenectomy was associated with a poor response (p=0.034). Patients who failed rituximab and had prior multiple treatments including splenectomy, had a poor outcome of further therapies. We conclude that rituximab is well tolerated and is useful in some patients with relapsed or refractory ITP; however, only about one-fifth of patients achieved sustained remissions. Patients refractory to rituximab had a poor response to further treatment.