case of t-cell lymphoproliferative disorder associated with hypereosinophilia with excellent response to mycophenolate mofetil

Hypereosinophilic syndrome [HES] is a group of rare blood disorders characterized by a persistent elevation of blood eosinophil count >/= 1.5 * 10[9]/L and clinical manifestations attributable to eosinophilia or tissue hypereosinophilia. Lymphocytic variant of HES [HES-L] is a known subtype according to World Health Organization classification. It is well documented in the literature that patients with HES-L are predisposed to develop T-cell lymphoma. We report a case of T-cell lymphoproliferation associated with hypereosinophilia, which has been successfully treated with mycophenolate mofetil, with resolution of skin lesions and normalization of eosinophil count and immunoglobulin E level. We believe this is a clinically relevant case since this is a rare disease with little known knowledge on its best treatment modality

Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR / ABL rearrangement

Expression of myeloid or T cell lymphoid in precursor B cell acute lymphoblastic leukemia [pre-B cell ALL], which is referred to as aberrant expression, is quite a common phenomenon. CD66c is a myeloid marker which has aberrant expression in pre-B cell ALL, with strong correlation with non-random genetic changes [BCR/ABL rearrangement]. Another leukemia associated marker [CD25] is frequently expressed in pre-B cell ALL. The frequency of CD25-expressing lymphoblasts has been found to be significantly higher in BCR/ABL-positive vs. BCR/ABL-negative patients. In a cohort of 103 patients diagnosed with pre-B cell ALL or biphenotypic leukemia and studied for expression of CD66c and CD25 at presentation, we evaluated the frequency of expression of either or both in BCR/ABL positive cases. Surface CD66c was expressed by 70 cases [68%] and CD25 was expressed by 33 cases [32%] while both were expressed together on 29 cases [28%]. BCR/ABL was positive in 18/103 patients. All BCR/ABL positive cases were positive for surface CD66c and CD25. Positivity for both leukemia-associated antigens CD66c and CD25 in combination can predict the presence of BCR/ABL rearrangement in pre-B cell ALL. While this finding does not replace the detection of BCR/ABL abnormality by cytogenetic or molecular techniques, it does provide an early and handy tool for prediction and management of high-risk cases of pre-B cell ALL, especially in centers with limited laboratory facilities

Validation of a modified cryopreservation method for leukemic blasts for flow cytometry assessment

Cryopreservation, a common method for storing human cells, has advantages when cells are used in retrospective studies of selected cell populations. Frozen lymphocytes can be used for tissue typing, for monitoring cell-mediated immunity, and for various immunological tests. Our report describes an efficient, simple and inexpensive method for cryopreservation of human acute leukemia cells. Leukemia cells from 20 newly diagnosed cases were frozen at -80°C after cryopreservation with 5% dimethysulfoxide and then assayed by flow cytometry for antigen expression determined by monoclonal antibodies at different time intervals. All cases had viability above 75% at presentation. After 4 weeks, 91% of pre-B ALL, 88% of T-ALL, 100% of AML, and 100% of biphenotypic aliquots had viability over 75%. Viability continued to be reliably above 75% at 6 weeks from cryopreservation. We confirm that the method does not significantly alter the viability of cells and it preserved the antigenic expression of leukemia cells

challenge of risk stratification in acute myeloid leukemia with normal karyotype

Cytogenetic aberrations have long been recognized as the most important prognostic variable in acute myeloid leukemia [AML] and are now a major stratification tool for post-remission therapy. Cytogenetics-based stratification improves survival. Patients with AML and normal cytogenetics, the largest single subgroup, have had a very heterogeneous outcome with standard chemotherapy in multiple clinical trials. Hence it is difficult to recommend a [one size fits all] kind of treatment for this heterogeneous population of AML patients. New emerging data from preclinical, retrospective, and large, randomized controlled studies indicate that in addition to cytogenetic abnormalities, many other molecular aberrations are operative in the response to treatment as well as in the risk of relapse. Such molecular markers are being tested for developing targeted therapies and may help in improved stratification of patients in the selection of post-remission therapy. Emerging evidence reveals that at the submicroscopic level, AML with normal cytogenetics may carry poor prognostic genetic lesions or [molecular signatures] as is the case with FLT3 mutations and overexpression of BAALC, ERG or MN1, or may have aberrations that predict better risk as is the case with isolated NPM1 or CEBPA mutations. Later studies have tried to explore the interaction of various prognostically important genes in this group of AML patients. The utility of the evolving data for bedside management of such patients is expected to improve with the wider application of modern tools, using the proposed clinical outcome models, and probably by development of a risk-scoring system based on the relative risk associated with each molecular aberration. The goals include identifying those patients most likely to benefit from upfront allogeneic HSCT and sparing good-prognosis patients from unnecessary transplant-related morbidity. The following is an outline of the most common molecular changes, their impact on the outcome of AML patients with normal cytogenetics and challenges in their wide scale application in risk stratification