Successful Early Outcome with Low-Dose (400 cGY) Total Body Irradiation in Combination with Busulfan and Fludarabine Myeloablative Conditioning Followed By Matched Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Non-Remission Acute Myelogeneous Leukemia with Diffuse Extramedullary Disease in Multiple Sites

Outcome after allogeneic stem cell transplantation (allo-SCT) is poor with 10-20% probability of long term survival in patients with acute myelogeneous leukemia (AML) not in remission at the time of transplant. The main cause of transplant failure in this high risk population is disease post-transplant relapse. We treated a 32 year-old male with undifferentiated AML (M0) who initially presented with leukocytosis, circulating blasts and a large anterior mediastinal mass abutting adjacent structures. A core biopsy of the mass revealed myeloid sarcoma. Patient developed respiratory distress requiring endotracheal intubation and mechanical ventilation. Cytogenetics revealed Hyperdiploid, 55, XY,+4,+6,+8,+9,+10,+11,+14,+19,+mar[12]/46,XY[14]. FLT3 ITD was positive. He did not respond to initial induction chemotherapy with 7+3 (daunorubicin 60 mg/m²/d and Cytarabine 100 mg/m²/d). He achieved morphologic and cytogenetic complete remission after re-induction with high dose cytarabine and mitoxantrone. He also received scheduled prophylactic triple intrathecal chemotherapies throughout his treatment course and started high dose cytarabine consolidation (HIDAC). His treatment courses were complicated by numerous medical problems, requiring a second prolonged hospitalization following third consolidation. He was intubated again due to diffuse alveolar hemorrhage. The patient was eventually discharged with tracheostomy collar and supplement oxygen, which was discontinued later on. A follow-up CT of chest showed increase in size of mediastinal mass but continuous CR in BM exam. While unrelated donor allogeneic SCT is in process, he received one course of decitabine. At the time of pre-transplant work-up, he relapsed of her AML first at his left conjunctivae and shortly after on his skin, presented with diffuse chloroma lesions on his trunk. He was treated with external radiation to his left eye with additional IT chemo (negative cytology). He underwent 10/10 HLA match unrelated donor allogeneic stem cell transplantation following PK-directed IV Busulfan with targeted AUC of 20,000 and Fludarabine 160 mg/m2 plus total body irradiation 200 cGY/d x 2 days. Skin lesions were active but bone marrow was in remission at the time of transplant. GVHD prophylaxis was tacrolimus and low dose methotrexate 5 mg/m²/d on days+1, +3, and +6 only. No ATG was given. His post-transplant course was relatively unremarkable. No major complications requiring re-admission to hospital occurred. His trach collar was kept thoughout his transplant and post-transplant courses due to tracheal stenosis. He achieved complete morphologic and cytogenetic remission with resolution all of his extramedullary leukemia including his mediastinal mass on day+100 evaluation. Currently he has been receving monthly 5-Azacitidine maintenance and clinically well on day+122. This case illustrates a successful early outcome after peripheral blood allogeneic stem cell transplantation using the combination of chemo-low dose radiation in a patient with non-remission AML with diffuse extra medullary disease. Optimum combination of radiation and chemotherapy in conditioning regimens may improve transplant outcomes in patients with non-remission AML and warrants prospective Phase I-II clinical trials.