Patient a year old man with RAEB and severe chronic

Patient 2, a 54-year-old man with RAEB 2, and severe chronic obstructive pulmonary disease, struggled through induction chemotherapy with daunorubicin plus cytarabine (DA) 3+10. Second DA 3+8 produced delayed hematopoietic recovery. CR1 was documented after course 1 and lasted 18 months. Relapse was normo/hypocellular with normal karyotype. He declined further intensive therapy and was considered unsuitable for allogeneic stem cell transplantation due to poor pulmonary and cardiac function. He was treated with oral melphalan 2mg daily for 11 weeks and achieved complete hematological response of 8 months duration. He has since been maintained on supportive care with 2-weekly red cell transfusions for over 12 months. Patient 3 presented at age 62 with RAEB 1 and a history of diabetes mellitus, hypertension, prostatic carcinoma and coronary artery by-pass graft. He achieved CRi (dysplastic) with DA 3+10. Delayed hematopoietic recovery after DA 3+8 prevented further consolidation chemotherapy. He relapsed after six months with normocellular RAEB 1 with normal karyotype. After five cycles of azacitidine, marrow examination showed transformation to AML (normal karyotype). Further intensive chemotherapy with ADE (daunorubicin, cytarabine, and etoposide) led to life threatening invasive fungal infection and myocardial infarction. Marrow examination was severely hypocellular but with <5% blasts. He remained heavily transfusion dependent and ten months later an increase in peripheral blasts was noted. In an attempt to improve hematopoietic function he was treated with melphalan 2mg daily for four weeks without side effects. No response was noted and melphalan was stopped. He was maintained on supportive care alone for 18 months with weekly red cell and platelet transfusions and frequent hospitalization for infection. Patient 4 a 60-year-old man presented with AML. Despite severe purchase thapsigargin he was treated with induction chemotherapy with DA 3+10, followed by DA 3+8 and MACE (mitoxantrone, cytarabine, amsacrine) consolidation on the Medical Research Council AML15 trial. Delayed hematopoietic recovery prevented the planned fourth course of chemotherapy. CR1 was documented after course 1 and lasted 17 months. Relapse was hypocellular RAEB 1 (10% blasts) with normal karyotype. He was treated with oral melphalan 2mg for 6 weeks without hematological response or complications requiring hospitalization as an in-patient. Eight weeks post melphalan on supportive care only, he demonstrated partial trilineage recovery. He became red cell transfusion independent with hemoglobin concentration maintained at >10g/dl. His platelet count rose from 5–12×10/l pre- and immediately post-melphalan to 65–70×10/l, and his neutrophils rose from 0.07–0.25×10/l to 0.36–1.13×10/l. Four weeks later, he commenced three cycles of Azacitidine, which were complicated by recurrent infections and progressive haematopoietic and clinical deterioration. He was maintained on supportive care for a further 8 months. Patient 5 was a 57-year-old male with AML. He tolerated only 2 courses of DA (3+10, followed by 3+8) chemotherapy due to hepatic candidiasis. He relapsed after CR1 duration of 6 years and was re-induced with 2 courses of ADE (3+5+10, followed by 3+5+8) then intermediate dose cytarabine (1.5g/m×6 doses) achieving CR2. Allogeneic stem cell transplant was discussed but given significant cardiac and respiratory comorbidity was declined by both physician and patient. CR2 duration was 3 years. At second relapse he declined further intensive chemotherapy. He commenced melphalan 2mg daily and received 7 weeks of treatment. He was admitted with neutropenic sepsis twice in the subsequent 4 weeks, declined further active treatment and died peacefully in hospice care. Patient 6 was a 69-year-old female with no co-morbid conditions presenting with pancytopenia. RAEB-2 was diagnosed and she was treated with DA 3+10 then DA 3+8. Prolonged hematopoietic regeneration did not allow a consolidation block. CR1 duration was 12 months and relapse was again hypocellular with a normal karyotype and 16% bone marrow blasts. She declined re-induction with intensive chemotherapy and commenced low-dose oral melphalan 2mg daily for 12 weeks. She obtained a complete hematological response with no toxicity, one red cell transfusion and no hospitalization. Bone marrow examination confirmed CR2 with 1.9% bone marrow blasts. She remains in CR2 of 3 months duration.