Prevalence of the BCR/ABL fusion gene and T cell stimulation capacity of dendritic cells in chronic myelogenous leukemia.

Dendritic cell (DC) vaccines are promising for immunotherapy, and their production using CD34+ hematopoietic stem cells (HPSCs) from patients with chronic myelogenous leukemia (CML) and healthy donors is well established. However, the generation of CD1a+CD14- DCs and their functional properties in patients with CML remain elusive. Here, we aimed to study the biology of DCs generated from CD34-/low HPSCs and evaluate the status of their BCR/ABL translocation, ability to stimulate T cells, and capacity of endocytosis compared to DCs derived from CD34+ HPSCs from both patients with CML and healthy donors. CD1a+CD14- DCs were generated from CD34-/low HPSCs and evaluated morphologically and functionally. CD34+ cells are frequently selected for transplantation and the entire CD34-/low HPSC fraction is wasted. Here, we anticipated the CD34- HPSC subset to constitute an invaluable source for acquiring DCs for immunotherapy. CD34+ and CD34- HPSCs were sorted from the bone marrow samples of CML patients and healthy donors and differentiated ex vivo in a similar way. DCs from CD34-Lin- and CD34+Lin- HPSCs expressed comparable surface markers (CD80, CD83, CD86, HLA-DR, CD40, and CD54). Functional analysis revealed that DCs acquired from both subsets retained a potent allogeneic T cell stimulatory capacity and an efficient phagocytic ability and showed a similar BCR/ABL translocation status. In conclusion, DCs were successfully differentiated from the CD34-Lin- cell subset and showed potent functional capacities, indicating their potential for application in immunotherapy and basic research.

Hepatotoxicity induced by horse ATG and reversed by rabbit ATG: a case report.

BACKGROUND: The use of antilymphocyte agents has improved patient and graft survival in hematopoietic stem cell and solid organ transplantation but has been associated with the development of short-term toxicities as well as long-term complications. CASE PRESENTATION: We report a young female with Fanconi anemia who received antithymocyte globulin as part of the conditioning regimen prior to her planned allogeneic hematopoietic stem cell transplant at King Faisal Specialist Hospital and Research Centre in Riyadh. She developed sudden and severe hepatotoxicity after receiving the first dose of horse antithymocyte globulin, manifested by marked elevation of serum transaminases and mild elevation of serum bilirubin level. Immediately after withdrawal of the offending agent and shifting to the rabbit form of antithymocyte globulin, the gross liver dysfunction started to subside and the hepatic profile results returned to the pre-transplant levels few weeks later. The patient had her allogeneic hematopoietic stem cell transplant as planned without any further hepatic complications. After having a successful allograft, she was discharged from the stem cell transplant unit. During her follow up at the outpatient clinic, the patient remained very well and no major complication was encountered. CONCLUSION: Hepatotoxicity related to the utilization of antithymocyte globulin varies considerably in severity and may be transient or long standing. There may be individual or population based susceptibilities to the development of side effects and these adverse reactions may also vary with the choice of the agent used. Encountering adverse effects with one type of antithymocyte agents should not discourage clinicians from shifting to another type in situations where continuation of the drug is vital.

del(6)(p23) in two cases of de novo AML--a new recurrent primary chromosome abnormality.

OBJECTIVE: Previously, deletion 6p23 was generally reported in therapy-related secondary acute myeloid leukemia (AML) as part of complex karyotypes. In this report, we present two young adult patients with de novo AML-M2 and a terminal deletion 6p23 as a sole primary abnormality, confirmed by chromosome 6 specific subtelomeric probes. METHODS: Two female patients 35 and 20 yr of age presented with anemia, but no bleeding, infections, lymphadenopathy or organomegaly. Morphological, immunophenotyping, chromosome and fluorescent in situ hybridization (FISH) analysis was performed on bone marrow aspirate cells. RESULTS: A diagnosis of AML-M2 was confirmed in both patients by morphological and immunophenotyping studies. Chromosome analysis in case no. 1 showed deletion 6p23 in 20% of metaphases whereas in case no. 2 the deletion 6p23 was present in 100% metaphases. FISH analysis confirmed the deletion as terminal in both cases. The DEK oncogene at 6p23 in both cases was found not to be deleted. CONCLUSION: To our knowledge, deletion 6p23 as a sole primary abnormality was reported in only one case. The common morphological, immunophenotypic, and cytogenetic features in our two patients strongly support a separate new entity of de novo AML with deletion 6p23.

Acute tumor lysis syndrome secondary to hydroxyurea in acute myeloid leukemia.

OBJECTIVE: To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment. CASE SUMMARY: A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS. DISCUSSION: ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients. CONCLUSIONS: Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.