The mechanism leading to the gelatinous
The mechanism leading to the gelatinous transformation may involve inhibition of tyrosine kinase activity by tyrosine kinase inhibitors (TKI) leading to blockage of downstream signal pathways, affecting extracellular matrix deposition, adipocyte differentiation and angiogenesis. Moreover, the catabolic processes in leukemia may also lead to the production of hyaluronic antimalaria medication by leukemic cells. Dasatinib, a more potent second generation TKI, has been used for treatment of chronic myeloid leukemia as well as Ph+ ALL. It can cause cytopenias but gelatinous transformation is an unusual event. Though our patient also received prednisolone, vincristine, daunorubicin and asparaginase as a part of induction therapy for ALL alongwith dasatinib, we conclude that the gelatinous transformation and non-recovery of marrow probably was due to dasatinib, analogous to that caused by imatinib as reported in previous studies. Pancytopenia can develop following treatment with TKIs and bone marrow examination may be required for definitive diagnosis.
Conflict of interest
Low dose melphalan is a highly effective and well-tolerated treatment in a selected group of patients with Acute Myeloid Leukemia (AML) or Refractory Anemia with Excess Blasts (RAEB) unfit for intensive chemotherapy. Durable complete remissions (CR) have usually been obtained in patients with hypocellular marrow and normal cytogenetics, with a typical CR1 lasting 12 months A total of 98 patients have been reported in 6 studies, of which 75 had a diagnosis of RAEB and 23 a diagnosis of AML (secondary or with dysplasia). No patient had received prior intensive chemotherapy, but 8 patients had received low dose chemotherapy (cytarabine, danazol or mercaptopurine) prior to melphalan treatment. Fifty one responses were recorded of which 31 were complete remissions. Ease of administration, good side effect profile and low cost make it an attractive option. Melphalan is a cytotoxic alkylating agent, although the mechanism of action in MDS/AML remains unclear. Mild worsening of baseline cytopenias precedes responses but the pharmacodynamics is not typical for conventional chemotherapeutic agents in these disorders. All studies described used a schedule of 2mg daily oral melphalan. Re-treatment usually produces a second CR of shorter duration. Further re-treatment is rarely able to produce CR3 and at the point of chemoresistance most patients have a 17p deletion/TP53 mutation This observation should perhaps restrict melphalan to elderly patients with RAEB/AML and/or those whose goal for treatment is primarily improved quality of life. We have now treated six patients with low dose melphalan,who presented at initial diagnosis (between 2005 and 2011) with AML/RAEB, a hypocellular marrow and normal karyotype and who had relapsed following initial induction of complete remission with standard intensive chemotherapy. Bone marrow trephine biopsy cellularity was assessed in a single diagnostic laboratory as low for the patient\'s age and was always <50%. No patients had molecular analyses performed. All were deemed either unfit for re-induction with intensive chemotherapy or declined intensive treatment. Verbal informed consent was given in all cases. Three patients achieved a complete hematological response to oral melphalan (). Patient 1 was aged 73 years with AML. Her initial chemotherapy was daunorubicin, clofarabine (DClo) and gemtuzumab ozogamycin on the Leukemia Research Fund AML16 trial. CR1 was documented after course 1. Following course 2 (DClo only) she developed severe sepsis and acute renal injury requiring temporary dialysis. Further consolidation chemotherapy was deemed unsafe. CR1 lasted 17 months. The relapse marrow was hypocellular with a normal karyotype. She declined further intensive chemotherapy. She obtained a complete hematological response with eight weeks of oral melphalan 2mg daily without side effects. Hematological relapse was noted after 12 months and another complete hematological response was obtained with further re-induction with melphalan. This lasted for 6 months and attempted re-induction with melphalan was then unsuccessful. She has received supportive care with 3-weekly red cell and clinically-driven platelet transfusions.