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Biomedical subjects

J D Cotelingam

Publications and source records attributed to J D Cotelingam.

At least 19 recordsLinked to original sources

Allosensitization in patients receiving multiple blood transfusions.

Extended antigen (C, E, K) matching decreased the incidence of alloantibody (alloAB) and autoantibody (autoAB) formation, in addition to eliminating transfusion reactions in the multiply transfused sickle cell disease patients. AlloAB formation possibly transforms the immune system into a hyperactive state leading to further and earlier alloAB and autoAB formation. However, additional CEK matching results in marked overuse of Rh-negative packed red blood cell (pRBC) units, 30 minutes' extra time of a skilled technologist, and 153 dollars extra CEK reagent cost per unit to find CEK-matched pRBCs for every transfusion for these multiply transfused patients.

Adolescent↗

Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases.

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of >/=50% erythroid of all nucleated cells and M6A with >/=30% myeloblasts/nonerythroid component; M6B with >/=30% proerythroblasts/erythroid component; and M6C with >/=30% myeloblasts and >/=30% proerythroblasts. The demographics, cell type distribution, and survival (mean +/- sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 +/- 3.6 months) versus M6A (25 +/- 28 months), P< 0. 002, and M6C (10 +/- 13 months) versus M6A, P< 0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies.

Adult↗

Effects of multidrug resistance gene expression in acute erythroleukemia.

Acute erythroleukemia is a relatively rare disorder of a multilineal nature. Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy. Forty-eight archival cases of acute erythroleukemia, subtypes M6a (the traditional FAB-M6), M6b (pure erythroleukemia), and M6c (>30% myeloblasts and >30% pronormoblasts by FAB exclusion criteria), were evaluated for multidrug resistance gene (MDR-1) status. Findings were correlated with clinical course and karyotypes. Immunohistochemical stain for the protein product of MDR-1, P-glycoprotein, was variably positive in 11 of 23 patients with M6a, as well as in all of the patients with M6b (strongly positive) and M6c (weakly positive). P-glycoprotein expression positively correlated with unfavorable cytogenetic aberrations, poor response to chemotherapeutic agents, and short survival. Most significant was that P-glycoprotein expression demonstrated a negative additive effect on response to treatment and prognosis with unfavorable cytogenetic anomalies. P-glycoprotein expression and multiple cytogenetic anomalies most probably contribute to the resistance to chemotherapy and poor survival characteristic of the patients with M6b (mean survival, 3.15 +/- 4.2 mo) and M6c (mean survival, 10.5 +/- 12.7 mo). Because patients with M6b and M6c have increased numbers of pronormoblasts in their bone marrow and past chemotherapeutic attempts have failed, chemotherapy directed at these cells is appropriate. Additional therapy directed toward the MDR-1 gene and its protein product seems indicated from our findings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

T-cell-rich B-cell lymphoma and Epstein-Barr virus infection of the uterus in a postmenopausal patient with an intrauterine contraceptive device in place for over 20 years.

Although secondary involvement of the female genital tract occurs in up to 40% of cases of disseminated lymphomas, lymphomas presenting with primary female genital tract symptomatology are very unusual. We report a case of T-cell-rich B-cell lymphoma (TCRBCL) arising in the uterine corpus of a 57-year-old female who carried an intrauterine contraceptive device (IUD) for over 20 years. Malignant lymphoid cells expressed the Epstein-Barr virus (EBV) late membrane protein (LMP), a feature described in TCRBCL but not previously reported in primary uterine lymphomas. To our knowledge, this is the first reported case of a TCRBCL of the uterus.

DNA, Neoplasm↗

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis.

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.

Adult↗

Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases.

BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare immunoproliferative disorder, the clinical course of which varies. In related B-cell neoplasms, such as multiple myeloma and chronic lymphocytic leukemia, the histologic features of bone marrow are considered to be of prognostic relevance. METHODS: To assess the prognostic features of WM, the authors reviewed the clinical and pathologic features of 22 patients. Bone marrow aspirates and core biopsies were available for each case. Immunostains for a panel of hematopoietic markers as well as p53 and proliferating cell nuclear antigen (PCNA) were performed. RESULTS: There were 14 males and 8 females, with a mean age of 60 years. At presentation, two histologic subtypes, lymphoplasmacytoid (73%) and lymphoplasmacytic (27%), were observed. Four patterns of bone marrow infiltration were delineated: diffuse (45%), nodular-interstitial (22%), mixed paratrabecular-nodular (20%), and paratrabecular (13%). In 11 patients, the infiltrate occupied greater than 70% of the bone marrow; in 8 patients, 30-70%; and in 3 patients, less than 30%. PCNA reactivity was observed in 58% of cases and p53 reactivity in 21%. Ten patients died of disease with an average survival of 84 months. The remaining 12 patients were alive with disease at last follow-up. The pretreatment parameters that were correlated with shorter survival were hemoglobin, white blood cell count, platelet count, splenomegaly, lymphadenopathy, and serum immunoglobulin M level. CONCLUSIONS: The findings of this study suggest that some pretreatment parameters, such as cytopenia, serum immunoglobulin M level, splenomegaly, and lymphadenopathy, correlate with poor prognosis for patients with WM. In contrast, histologic features and expression of p53 and PCNA did not correlate significantly with survival.

Adult↗

Comparative utility of diagnostic bone-marrow components: a 10-year study.

Ten years of cumulative experience represented by 4,902 consecutive diagnostic bone-marrow examinations at a tertiary care and referral center were reviewed to assess the value of specific components. While it has been shown previously that the information obtained from each component is generally complementary, the inclusion of some or all components may vary between institutions. The components studied included aspirate smears, clot sections, biopsy cores, and touch imprints of biopsy and clot sections. Three clinical presentations accounted for the majority of cases: staging for carcinoma or lymphoma, cytopenias, and acute leukemia. We conclude that bilateral aspirates with biopsies are required for diagnosis in staging of neoplasms and that a unilateral aspirate with biopsy is sufficient to assess patients with cytopenia or leukemia. Only rarely were touch imprints of biopsy cores necessary to establish a diagnosis; however, their early availability prior to examining sections of the clot and core did provide immediate information, when positive, in the staging of patients with carcinoma. In a small percentage of staging and leukemia cases the diagnosis rested with the clot section alone. The findings in this study address common assumptions associated with routine diagnostic hematology and oncology procedures, and are important to both clinicians and pathologists concerned with accuracy, quality assurance, turnaround time, and cost containment.

Biopsy↗

Clinical aspects of expression of inversion 16 chromosomal fusion transcript CBFB/MYH11 in acute myelogenous leukemia subtype M1 with abnormal bone marrow eosinophilia.

The pericentric inversion of chromosome 16 (inv(16)(p12q22)) is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. It is increasingly appreciated as both a favorable prognostic factor and important guide to therapy. The breakpoints of the inversion have been cloned and a fusion transcript can be identified by RT-PCR. We expand upon our prior abstract of a case of AML subtype M1 with abnormal eosinophils that expressed the inversion 16 fusion transcript CBFB/MYH11. During remission, the transcript could not be detected. The patient relapsed twice during the first year after attaining a complete remission. Morphologically, the relapsed specimens were identical to the appearance of his diagnostic specimen. However, the CBFB/MYH11 fusion transcript was not detected in the relapsed specimen. We conclude that CBFB/MYH11 fusion transcript detection, as a surrogate for the favorable prognosis and treatment planning implied by inv(16) in AML M4Eo, should not be exclusively relied upon in AML M1 in the absence of prospective study of this specific (M1) category of AML. RT-PCR analysis should be correlated with cytogenetics when available and if used alone should be interpreted cautiously in cases of AML with atypical morphological features.

Aged↗

Acute megakaryoblastic leukemia following transient myeloproliferative disorder in a patient without Down syndrome.

Transient myeloproliferative disorder (TMD) and subsequent acute myeloid leukemia (AML) occur with increased frequency in infants and children with Down syndrome. TMD can also occur in phenotypically normal newborns. We describe the second case of a non-Down syndrome child with TMD who subsequently developed AML. Trisomy 21 karyotypic was restricted to hematopoietic cells in the blood and bone marrow. No other karyotypic abnormalities were found. Leukemic blasts showed megakaryoblastic features with immunophenotyping. This case shows that TMD in a child without Down syndrome may not be entirely benign. Close follow-up is warranted.

DNA, Neoplasm↗

Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease.

Discordant lymphomas are those in which two different histologic subtypes of non-Hodgkin's lymphoma are present simultaneously in the same patient at two or more separate disease sites. Discordance usually involves a lower grade follicular lymphoma in one anatomic site and a higher grade diffuse lesion elsewhere. A common type of discordance is seen in patients with a primary diagnosis of diffuse large-cell lymphoma (DLCL) who demonstrate bone marrow involvement by a lower grade lesion, such as a small cleaved cell or mixed small cleaved and large cell lymphoma. This study was undertaken to assess retrospectively the clinical implications of such bone marrow involvement, as well as the possible biologic mechanisms. Of the 59 DLCL cases studied, 20 (33.9%) showed evidence of bone marrow involvement, 14 of which were discordant (70%). The most significant findings included the following: Overall treatment responses and survivals in discordant patients with predominantly small cleaved cells in the marrow were similar to those in patients with no marrow involvement (mean survivals, 47.7 and 49 months, respectively), and were significantly longer than in patients with concordant marrow involvement (mean survival, 13.1 months, P < .05). Patients with discordant marrow infiltrates composed of a mixed cell population tended to do as poorly as those with concordant involvement. No clear-cut pattern of relapse in discordant patients was found, but persistence of small cleaved cells in some was reminiscent of lower grade B-cell lesions. Other features associated with lower grade lesions included older age, less incidence of central nervous system involvement, and lesser extent and proportion of marrow infiltration. Finally, in approximately half the cases with discordant involvement, lymphoma was present unilaterally, emphasizing the need to perform bilateral biopsies for staging.

Adult↗