Acute lymphocytic leukemia relapsed

Children with acute lymphocytic leukemia (ALL) are classified according to their risk of relapse. Risk assessment is an important factor in the selection of treatment. The goal is to match treatment to risk and minimize over- or undertreatment. 

VX-680 (71) is the most advanced pyrazole class Aurora inhibitor, disclosed by Vertex. The compound is reportedly in Phase I clinical development in patients with relapsed or refractory acute myelogenous leukemia, myelodys-plastic syndrome, acute lymphocytic leukemia, and chronic myelogenous leukemia and in Phase II for advanced colorectal cancer [172,173]. VX 680 (71) was a potent inhibitor of all three Aurora kinase enzymes (Aurora-A Ki = 0.0006 p.M Aurora-B Ki = 0.018 p,M Aurora-C Ki = 0.0046 tiM). Com-... 

The existence of the blood-brain barrier is an important consideration in the chemotherapy of neoplastic diseases of the brain or meninges. Poor drug penetration into the CNS has been a major cause of treatment failure in acute lymphocytic leukemia in children. Treatment programs for this disease now routinely employ craniospinal irradiation and intrathecally administered methotrexate as prophylactic measures for the prevention of relapses. The testes also are organs in which inadequate antitumor drug distribution can be a cause of relapse of an otherwise responsive tumor. 

Other routes of administration can be employed in certain situations. Methotrexate and cytarabine are given intrathecally or intraventricularly to prevent relapses in the meninges in acute lymphocytic leukemia and to treat carcinomatous meningitis. Thiotepa and bleomycin have been administered by intravesical instillation to treat early bladder cancers. Fluorouracil can be applied topically for certain skin cancers. 

Annamycin, a semi-synthetic lipophilic doxorubicin analogue, capable of circumventing multidrug-resistance transporters, was incorporated in tween-containing liposomes. (34-36). Currently, this liposomal formulation is investigated in Phase II trials in patients with refractory or relapsed acute lymphocytic leukemia (37). 

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