BUSM News and Notes

Monthly newsletter providing updates of interest to the Boston University School of Medicine community

Dr. Dorfman legacy to pathology: beyond Rosai-Dorfman disease

Ronald F. Dorfman (1923-2012), an Emeritus Professor of Pathology at the Stanford University School of Medicine, had significant input in advancing the study of diseases of hematopoietic cells and the lymph nodes, which included identifying a disease that has been named after him. Dr. Dorfman was one of the founders of the field of Hematopathology, and, with Dr. Costan Berard, founded the Society of Hematopathology in 1981, serving as its president from 1982 through 1984, and published a classification of non-Hodgkin lymphomas in 1974, which was a variant of the Rappaport classification

Humphrey Center News: Fall 1988 v. 3, no. 2

Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression

Between March 27, 1989 and December 31, 1997, 1316 kidney transplantations alone were performed under tacrolimus-based immunosuppression at our center. Posttransplant lymphoproliferative disorders (PTLD) developed in 25 (1.9%) cases; the incidence in adults was 1.2% (15/1217), whereas in pediatric patients it was 10.1% (10/99; P<.0001). PTLD was diagnosed 21.0±22.5 months after transplantation, 25.0±24.7 months in adults and 14.4±18.2 months in pediatric patients. Of the 4 adult cases in whom both the donor and recipient Epstein Barr virus (EBV) serologies were known, 2 (50%) were seropositive donor → seronegative recipient. Of 7 pediatric cases in whom both the donor and recipient EBV serologies were known, 6 (86%) were EBV seropositive donor → seronegative recipient. Acute rejection was observed before the diagnosis of PTLD in 8 (53%) of 15 adults and 3 (30%) of 10 pediatric patients. Initial treatment of PTLD included a marked decrease or cessation of immunosuppression with concomitant ganciclovir therapy; two adults and two pediatric patients required chemotherapy. With a mean follow-up of 24.9 ±30.1 months after transplantation, the 1- and 5-year actuarial patient and graft survival rates in adults were 93% and 86%, and 80% and 60%, respectively. Two adults died, 3.7 and 46.2 months after transplantation, of complications related to PTLD, and 10 (including the 2 deaths) lost their allograft 3.7-84.7 months after transplantation. In children, the 1- and 5-year actuarial patient and graft survival rates were 100% and 100%, and 100% and 89%, respectively. No child died; one child lost his allograft 41.3 months after transplantation. One child had presumed recurrent PTLD that responded to discontinuation of tacrolimus and reinitiation of antiviral therapy. The mean serum creatinine level in adults was 2.5±1.2 mg/dl, and in children, it was 1.3±0.6 mg/dl. Under tacrolimus-based immunosuppression, PTLD is less common after renal transplantation in adults than in children, but PTLD in children is associated with more favorable outcomes than in adults

Benign TdT-positive cells in pediatric and adult lymph nodes: a potential diagnostic pitfall

Benign TdT-positive cells have been documented in a variety of non-hematopoietic tissues. Scant data are however available on their presence in non-neoplastic lymph nodes. This study is aimed to: (i) characterize the presence/distribution of benign TdT-positive cells in pediatric and adult reactive lymph nodes; (ii) define the phenotype and nature of such elements. This retrospective study considered 141 reactive lymph nodes from pediatric and adult patients without history of neoplastic disease. TdT-positive cells were characterized by immunohistochemical and morphometric analyses and their presence was correlated with the clinical-pathological features. The nature of TdT-positive cells was investigated by: (i) double immunostaining for early lymphoid cell markers; and (ii) assessment of TdT expression in fetal lymph nodes. Sparse TdT-positive cells were documented in all pediatric cases and in most (76%) adult lymph nodes. TdT-positive cell density was higher in children than adults (15.9/mm2 versus 8.6/mm2; P<.05). TdT positivity did not correlate with any clinical and histological parameter and double immunostaining disclosed a phenotype compatible with early lymphoid precursors (positivity for CD34, CD10 and variable expression of CD7). A very high TdT-positive cell density (802.4/mm2) was reported in all fetal lymph nodes. In conclusion, TdT-positive cells are a common finding in pediatric and adult lymph nodes. The interstitial distribution and low number of such cells allows for the differential diagnosis with precursor lymphoid neoplasms. The high density in fetal lymph nodes and the phenotype of such cells suggest their belonging to an immature lymphoid subset gradually decreasing with age

Relation of common ABL kinase domain mutations with resistance to Tyrosine Kinase Inhibiters in patients with Chronic Myeloid Leukemia in Middle Euphrates of Iraq

Background: Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease, associated with a reciprocal translocation between chromosomes 9 and chromosome 22, lead to the formation of the BCRABL fusion gene (Philadelphia chromosome). This fusion gene is believed to play golden role in the initial development of CML with constitutive tyrosine kinase activation. Successful use of tyrosine kinase inhibiters (TKIs) play a role in improve survival and increase prevalence of CML, but un fortunately mutations in the BCR-ABL kinase domain may cause, or contribute to increase, resistance to TKIs in CML patients. . Objective: This study was designed to assess the association of five most common BCR-ABL kinase domain mutations (T315I, M351T, E255K, M244V and E255V) with resistance state of CML patients on TKIs in Iraqi Middle Euphrates region. Patients and methods: A retrospective case-control study in which 85 patients with chronic myeloid leukemia in chronic phase (45 patients as cases group and 40 patient as control group) were selected from three hemato-oncology centers in middle Euphrates in Iraq during the period from January 2016 till October 2016 out of a total of 240 CML patients (108 male and 132 female) who were registered during this period in these three centers and all patients on TKI (Imatinib and Nilotinib). Venous blood sampling done for BCRABL kinase domain mutations screening. Results: four patients from cases group (4/45) were carriers of one of five selected ABL kinase domain mutations and no one of control group. T315I mutation was detected in 3/45 (6.6 %) of resistant patients, with a significant risk association to develop resistance to TKI therapy (odd ratio and C. I.) (6.67, 0.3340 - 133.2255). E255V was detected in 1/45 (2.2 %) and also had significant risk association to develop resistance to TKIs (odd ratio, C.I.) (2.73, 0.1081 -68.9424). No one of these mutations had significance correlation with demographic or hematological features. M351T, E255K and M244V were not detected in any one of our study groups CML patients. Conclusions: T315I and E255V among five ABL kinas domain mutations were detected in our CML patients with resistance to TKIs. All of them may play a role in development variable degree of resistance to first and second generation TKIs weather primary or secondary.T315I mutation is most common mutation within BCR-ABL domain kinase gene

Determining the Role of Point-of-Care Hemoglobin Testing in the Resuscitation of Acutely Hemorrhaging Patients

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb between 7-10 g/dL, intensivists should feel comfortable making decisions related to transfusion therapy without waiting for the CBC result