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Biomedical subjects

F R Dick

Publications and source records attributed to F R Dick.

At least 37 records · Page 2Linked to original sources

Long-term relapse-free survival in adult acute lymphoblastic leukemia.

An intensive treatment program with curative intent was designed for adults with acute lymphoblastic leukemia (ALL). Forty-eight consecutive patients were treated with this protocol and 39 (81%) obtained a complete remission. Although the complete remission rate was high for patients with both null- and T-cell disease, those with null-cell leukemia had a significantly greater median duration of remission (greater than 306 weeks) than patients with T-cell disease (62 weeks). The median survival by life-table analysis for the 48 patients is projected to be greater than 310 weeks, and five patients have finished the 3-year treatment program and have been off therapy for 1-3 years without recurrence of disease. Classification of adult ALL by immune marker status is an important and easily done pretherapy maneuver that identifies subsets of patients with a significantly different prognosis when treated with the protocol described in this study. Those patients for whom leukemic cells had T-cell characteristics had a short median duration of remission. Most importantly, this treatment protocol identifies by therapeutic response a subset of adult patients with ALL whose leukemic blasts are characterized by the absence of immunological markers and who appear, in substantial proportion, to be potentially curable.

Actuarial Analysis↗

Malignant lymphoma, diffuse mixed small and large cell. A clinicopathologic study of 47 cases.

The clinical and pathologic features of 47 cases of malignant lymphoma, diffuse mixed small and large cell (diffuse mixed lymphoma) are described. Diffuse mixed lymphomas contained approximately equal numbers of small and large cells (30-70%) and comprised 6% of all non-Hodgkin's lymphomas. They occurred in middle-aged and elderly patients (median age = 63 years), showed a female predominance, and were clinically advanced at presentation. The majority of patients exhibited prominent extranodal disease, which frequently involved multiple unrelated sites and usually occurred in conjunction with nodal disease. A notable morphologic spectrum of lymphoma was seen within this series, including 20 cases of mixed small cleaved and large cell (with cleaved and noncleaved nuclei), eight cases of mixed small lymphocytic and large cell (transformed prolymphocytes and blast-like cells), and 12 cases of mixed small cell and large cell, "immunoblastic" lymphoma (with plasmacytoid, clear cell or hyperconvoluted features). There was no significant difference in response to treatment and survival between those cases with less than 50% large cells and those with greater than 50% large cells. The poorest treatment response appeared to be in patients with mixed small cell and large cell, "immunoblastic" lymphomas. Patients with diffuse mixed lymphoma appeared to show a favorable response to cyclphosphamide, Adriamycin, vincristine, and prednisone (CHOP) and an unfavorable response to other treatment modalities.

Aged↗

Central nervous system involvement as a presenting feature of acute monocytic leukemia: preceding leukemia by 12 months.

This report describes a patient who presented with a diffuse malignant central nervous system (CNS) process composed of cells with monocytic differentiation one year before the development of acute monocytic leukemia. A similar presentation has been documented for acute lymphocytic leukemia, but to the best of our knowledge, this is the first report to detail a diffuse CNS malignancy as the presenting symptom for acute monocytic leukemia.

Aged↗

Second lymphoid malignant neoplasms occurring in patients treated for Hodgkin's disease.

Patients who have been treated for Hodgkin's disease are at increased risk for second malignant neoplasms, particularly acute nonlymphoblastic leukemia and non-Hodgkin's lymphoid malignant neoplasms (NHLMs). We diagnosed five cases of NHLM in 242 patients initially treated for Hodgkin's disease between 1973 and 1980, giving a minimum incidence for this occurrence of 2.1%. The initial therapy for Hodgkin's disease, irradiation in three patients and chemotherapy in two patients, resulted in a complete remission in each case. The NHLM appeared 12, 13, 26, 30, and 54 months after the diagnosis of Hodgkin's disease. The cell type of NHLM and immunologic phenotype were as follows: large cell, immunoblastic T; large cell, immunoblastic null; large cell, cleaved and noncleaved B; large cell, cleaved and noncleaved (not studied); and lymphoblastic T. A review of 24 other cases of NHLMs, occurring in patients treated for Hodgkin's disease, reported in the literature, confirm the morphologic and immunologic heterogeneity. The poor response to therapy in our patients and those previously described demonstrate the seriousness of this phenomenon.

Adolescent↗

Predicting therapeutic outcome in patients with diffuse histiocytic lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP).

Seventy-five patients with diffuse histiocytic lymphoma (DHL) ranging in age from 33 to 94 years were treated with cyclophosphamide, Adriamycin, vincristine and prednisone (CHOP). Thirty-eight patients (51%) achieved complete remission, but nine of these patients relapsed after remission lasting one to 23 months (median time to relapse, four months). We used multivariate analysis to identify those characteristics that significantly affected treatment outcome. The chances for complete remission were adversely affected by DHL appearing after histologic conversion from another lymphoma (P = 0.006), the presence of systemic symptoms (P = 0.24), and not having the large noncleaved (LNC) histologic subtype (P = 0.40). The chance for relapse from complete remission was increased only by the presence of systemic symptoms (P = 0.042). Overall survival was adversely affected by the presence of bone marrow involvement (P = 0.002), having other than LNC histologic subtype (P = .010), and the presence of systemic symptoms (P = 0.043). It appears that patients whose DHL appears de novo and who also are symptom status A (70% long-term disease-free survival) or have the LNC histologic subtype (67% long-term disease-free survival) have an excellent outlook when treated with CHOP at the doses used in this study. However, patients with B symptoms (16% long-term disease-free survival), histologic conversion to DHL (8% long-term disease-free survival), previous chemotherapy (8% long-term disease-free survival), and bone marrow involvement (8% long-term disease-free survival) respond poorly and for these patients other treatments need to be identified. In addition, patients with B symptoms who achieve complete remission with CHOP are at high risk to relapse (59% relapse rate) and should be considered for "intensification" therapy after complete remission is documented.

Adult↗

Diagnostic concurrence in the subclassification of adult acute leukemia using French-American-British criteria.

Using FAB criteria, we retrospectively classified 195 adult acute leukemia cases seen over a six-year period. Acute lymphoblastic leukemia (ALL) was separated from acute nonlymphoblastic leukemia (ANLL) by negative peroxidase. The dysmyelopoietic syndrome was separated from ANLL when the percentage of immature leukemic cells was less than 30%. The 55 cases of ALL and 140 cases of ANLL thus defined were initially independently subclassified with Wright's stained smears by three observers. Cases were then jointly reviewed by using all available information, and a final consensus diagnosis was reached. For ALL, there was complete agreement (of initial independent observations) about subtype in 32 of 55 (58%); for only one case was there total disagreement. For ANLL there was complete agreement in 89 of 140 (64%) and total disagreement in 5 of 140 (4%). Frequent disagreement of independent observations with the consensus diagnosis were L1 interpreted as 12, M5 interpreted as M4, L3 interpreted as L2, L2 interpreted as L1, M1 interpreted as M2 and M4 interpreted as M5. Although there appears to be variation between observers, all but 6 of 195 cases had at least two observers in agreement. Disagreement appeared to be partly based on varying interpretations of subjective criteria and partly on the variability in determining percentages of cell types present. The use of nonspecific esterase stain or lysozyme appeared to improve diagnostic agreement over that observed using Wright's stained slides alone in approximately 5% of cases of ANLL.

Esterases↗

Hodgkin's disease presenting as a thyroid mass.

Extranodal presentations of Hodgkin's disease are relatively unusual, and the presentation of the disease as a thyroid mass is rare. The patient described here had an enlarging thyroid mass over a year and was treated for some months with levothyroxine sodium (levothroid, Synthroid) suppressive therapy, with no results. Clinical staging after initial surgery revealed stage IIIA2 Hodgkin's disease, and combination chemotherapy was immediately begun.

Adult↗

Results of aggressive chemotherapy for acute nonlymphoblastic leukemia in adults.

Sixty-five patients with acute nonlymphoblastic leukemia, ranging in age from 16 to 73 years (median, 54), were treated with thioguanine, cytarabine, daunorubicin, prednisone, and vincristine to induce complete remission. Remission was maintained with monthly 5-day courses of cytarabine and thioguanine for 4 years. Of the entire group, 57% achieved complete remission and 29% died in the first 30 days of treatment. The median remission duration was 15 months, with 20% of the complete responders predicted to remain in complete remission for 4 years. No primary central nervous system relapses have occurred. Of six variables examined by multivariate analysis, only age was predictive of remission success. Before analysis, the patients were divided into groups by age: group 1--ages 16-42 years (n = 17); group 2--ages 43-59 years (n = 25); and group 3--ages 60-73 years (n = 23). Complete remission rates were 76% in group 1, 64% in group 2, and 35% in group 3 (P = 0.002). Lower remission rates for older patients resulted from more early deaths rather than resistant disease. Age and LDH levels affected remission duration. The median complete remission duration was 48 months in group 1 and 10 months in groups 2 and 3 (P = 0.004). In group 1, 41% of patients achieving complete remission are predicted to remain in complete remission for 4 years. We concluded that this five-drug induction regimen is highly effective for induction therapy in younger adults with acute nonlymphoblastic leukemia. The results in patients greater than or equal to 60 years of age are less satisfactory due to a lower remission rate and greater chance of early death. Furthermore, these results demonstrate that the program as described results in a longer duration of complete remission for patients of younger age.

Acute Disease↗

The effects of anti-leukemic therapy on gonadal histology in adult males.

Testicular histologic findings in 29 male patients who died of acute leukemia or blastic phase of chronic myelogenous leukemia are reviewed to evaluate the effect of therapy on morphology. Four histologic groups were identified that correlated with the duration of treatment: (1) normal testes associated with no therapy or therapy for less than 30 days; (2) maturation arrest in those treated for five days to 40 months; (3) hypospermatogenesis in those treated from 17 days to 84 months; and (4) Sertoli cells only in those treated from between three and 63 months. These histologic patterns correlated more with the duration of therapy than the type of anti-leukemic therapy used. There was some variability in the histologic effects among individuals receiving comparable durations and types of chemotherapy. In many patients who received extensive therapy, spermatogonia remain which may allow recovery of spermatogenesis and fertility.

Adult↗

Hypoplastic acute leukemia.

There have been few reports of acute leukemia presenting with a hypocellular bone marrow. All patients diagnosed as having acute leukemia were identified during a recent six-year interval who had blast cells plus promyelocytes of greater than 30% and marrow cellularity of needle biopsy less than or equal to 50%. Of 195 patients analyzed, 15 (7.7%) fulfilled the criteria. Ten patients were men and five women; the median age was 68 years with a range of 40-82. Seven complained of fatigue of 6-12 months duration, five were seen with occult infection, and three were asymptomatic. Hepatosplenomegaly was absent in 93% and none had lymphadenopathy. Fourteen patients were pancytopenic with median leukocyte count at presentation of 1.5 X 10(9)/liter, hemoglobin of 9.0 g/dl, and platelet count of 55 X 10(9)/liter. Circulating blast cells were not observed in ten patients; in the other five they were less than 0.7 X 10(9)/liter. The morphology of all cases appeared myeloid and Auer rods were seen in three patients; however, in one the peroxidase was negative. Classification according to FAB criteria revealed ten to be M1, three to be M2, one M4, and one L2. Median survival of the entire group was seven months. Of seven patients receiving no chemotherapy, two survived longer than 1 year (14, 24.5 months), one is alive at 7+ months, and the median survival was seven months. Eight patients with life-threatening complications received various combination regimens including an anthracycline, cytosine arabinoside, 6-thioguanine, vincristine, and prednisone. Five died of treatment complications; two achieved durable complete remission and are free of disease at 17 and 27 months. It can be concluded that hypoplastic acute leukemia is a distinct nosologic entity affecting primarily older patients with myeloid leukemia. Remission induction therapy in patients who are seriously ill has a low success rate, and in some patients prolonged survival is possible with supportive care alone.

Acute Disease↗

Analysis of the presenting features of adult acute leukemia: the French-American-British classification.

The authors have performed a clinical and statistical analysis of the presenting features of adult acute leukemia classified according to the French-American-British (FAB) hematopathologic criteria. Observations were made on 70 variables of history, physical examination, and laboratory examination recorded for 195 patients seen during a recent six year interval. The incidence of each category as determined by consensus of three observers was L1, 9%; L2, 17%; L3, 3%; M1, 21%; M2, 22%; M3, 5%; M4, 21%; M5, 4%; and M6 1%. there were recurring features of each FAB category and for aggregated categories (myeloid, lymphoid). Some groups such as L1, M3, M4, and M5 were characterized by many distinctive characteristics. In contrast, the L2, M1, and M2 categories had few distinctive characteristics, although L3 shared many features with the other lymphoid groups. The distinctness of the categories was quantitated by stepwise discriminant analysis. Using only a few computer-selected clinical variables, the authors classified patients into the correct FAB category with an accuracy of over 65% for some groups. The accuracy in discriminating between lymphoid and myeloid groups, the important therapeutic distinction, was 82%. This study demonstrates that many of the categories defined by the FAB criteria have characteristic clinical features at presentation.

Adult↗

Bone marrow chromosome abnormalities in breast cancer in patients following adjuvant chemotherapy.

Two patients developed acute bone marrow cancer following mastectomy and institution of alkylating agents as adjuvant chemotherapy. An aneuploid condition was observed in both cases, along with involvement of chromosomes 11 and 12 in structural rearrangements. Subsequent studies of 18 patients who had or had not received such therapy showed no evidence of chromosomal aberrations. However, the long-term effect of adjuvant chemotherapy in cancer patients is still of concern until additional information becomes available.

Adult↗

Clinical usefulness and reproducibility of histologic subclassification of advanced diffuse histiocytic lymphoma.

Thirty-one patients with stage III and IV diffuse histiocytic lymphoma (DHL) were treated uniformly with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP). The patients were subclassified independently by two hematopathologists into groups with predominantly large noncleaved cells (eight patients), predominantly large cleaved cells (seven patients), a mixture of large cleaved cells and large noncleaved cells (11 patients), tumors with the characteristics of immunoblastic sarcomas (two patients) and unclassified (three patients). The concurrence rate on applying the subclassification was 85 per cent. Survival in patients with large noncleaved cells was superior to that of the other patients as a group (p less than 0.001), and to that of those with large cleaved cells (p less than 0.05) and large cleaved and large noncleaved cells (p less than 0.025). All the patients with large noncleaved cells are alive and "off" therapy without evidence of progressive disease. This histologic subclassification seems to identify a subgroup of patients with advanced diffuse histiocytic lymphoma having large noncleaved cells who have an excellent prognosis when treated with CHOP.

Antineoplastic Agents↗

Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody.

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.

Adult↗

Cutaneous and nasal allergic responses in ragweed hay fever: lack of clinical and histopathologic correlations with late phase reactions.

The present study was designed to test the hypotheses that late cutaneous and nasal responses to allergen in patients with ragweed hay fever were human correlates of cutaneous basophil hypersensitivity, and that late responses in the nose and skin reflect similar pathogenesis. Forty-seven patients with ragweed hay fever were studied during a ragweed season for peripheral basophilia and clinical patterns reflecting late responses. Provocative nasal challenge, skin testing, and biopsy were carried out subsequently in 21 of the same patients during the winter months. Conclusions were as follows: (1) no histologic features distinguish positive from negative late skin reactions at 24 hr in patients with immediate wheal-and-flare responses; (2) cutaneous basophil hypersensitivity, i.e., tissue basophilia, is not a distinguishing feature of late skin responses in ragweed pollenosis; (3) seasonal peripheral basophilia was not found; (4) late responses in the nose were difficult to document objectively and did not correlate with late skin reactions; and (5) lymphocyte responses to antigen failed to correlate with late responses in either the nose or the skin.

Basophils↗

The lymph node in chronic lymphocytic leukemia.

Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic-histiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survival.

Adult↗

Diffuse histiocytic lymphoma complicating chronic lymphocytic leukemia.

Nine patients with chronic lymphocytic leukemia (CLL) who also developed diffuse histiocytic lymphoma (DH) are described. The incidence of patients with CLL developing DH was at least 3.3%. CLL existed for a median of 2 years before the diagnosis of DH. DH presented in 8 patients with abdominal symptoms and/or enlarging lymph nodes, spleen and liver. There were no consistent laboratory abnormalities associated with the onset of DH. In 4 of the patients the DH appeared to be localized. Eight of the 9 patients have died with a median survival of 2 months from the diagnosis of DH. Whether DH occurs as a result of "blastic transformation" of pre-existing CLL or is a second, unrelated malignancy is not certain. It is hypothesized that utilizing current therapies for DH might favorably influence survival.

Aged↗

Hodgkin's disease terminating in a T-cell immunoblastic leukemia.

A patient who developed an immunoblastic leukemia of T-cell type two and one half years after initial diagnosis of mixed cellularity Hodgkin's disease, stage IIIB, is described. The patient's course was characterized by an initial 15-months remission following radiation therapy. A relapse of Hodgkin's disease was treated with intensive chemotherapy. Thirteen months later the patient entered a rapid terminal course with multiple organ infiltrates and a leukemic peripheral blood. The leukemic phase was characterized by a 55,000 WGC with 48% immunoblasts, greater than 90% of which marked as T-cells. Although acute myelogenous leukemia, acute lymphocytic leukemia, lymphosarcoma cell leukemia and other tumors have been described in Hodgkin's disease after intensive therapy, this is the first report of the unusual association of a T-cell immunoblastic leukemia with Hodgkin's disease.

Antineoplastic Agents↗