Clinical chemotherapy refractoriness is characterized by resistance to multiple drugs. Multidrug resistance(MDR) is caused by over-reactivity of a unidirectional drug efflux pump, transmembrane glycoprotein(P-glycoprotein), which is encoded by the MDR1 gene. P-glycoprotein leads to increased drug efflux and decreased intracellular drug concentration. Clinical trials that attempt to reverse or modulate MDR have been done. Cyclosporin-A and verapamil are the most extensively studied agents and several trials of cyclosporin-A as a MDR modulator have been reported. We report a case of an 8-year-old girl with acute mixed type leukemia who failed to respond 3 times to remission-induction therapy. It led us to conclude she had multidrug resistance. We tried a fourth induction chemotherapy including cytarabine, idarubicin and 6-thioguanine to which cyclosporin-A was added. Then, she showed signs of severe bone marrow depression and fulminant perianal cellulitis. But she recovered and successfully achieved complete remission. The addition of cyclosporine could be useful in achieving complete remission for cases of acute leukemia that resist to usual chemotherapy. Futher observation including more cases will be needed to assess long-term survival and efficacy of adding cyclosporine.
Bone Marrow ; Cellulitis ; Child ; Cyclosporine ; Cytarabine ; Depression ; Drug Resistance ; Drug Resistance, Multiple ; Drug Therapy ; Female ; Humans ; Idarubicin ; Induction Chemotherapy ; Leukemia* ; P-Glycoprotein ; Thioguanine ; Verapamil

Bone marrow necrosis is a rare complication of a variety of diseases affecting the marrow. The cause and incidence are unknown, and reports of treatment response are rare. We describe a case of relapsed acute mixed type leukemia with bone marrow necrosis. The patient was a 10 year old female diagnosed with acute mixed type leukemia four years ago. She had been on second remission state for 1 year, presented with severe back pain, tenderness in lower extremities, low-grade fever and general weakness. Her level of serum lactic dehydrogenase on admission was increased. Bone marrow aspiration from both posterior iliac crest showed marrow necrosis. Subsequent examination showed the same feature. Hip MRI showed heterogenous low signal intensity in both iliac bone on T-1 weighted image and heterogenous high signal intensity on T-2 wieghted image. Remission induction therapy was started but she expired on 59th hospital day due to the complication of sepsis.
Back Pain ; Bone Marrow* ; Child ; Female ; Fever ; Hip ; Humans ; Incidence ; Leukemia* ; Lower Extremity ; Magnetic Resonance Imaging* ; Necrosis* ; Oxidoreductases ; Remission Induction ; Sepsis