Biomedical subjects

J B Cousar

Publications and source records attributed to J B Cousar.

At least 37 records · Page 2Linked to original sources

PubMed1993

Acquired immunodeficiency syndrome-like illness associated with systemic Mycoplasma fermentans infection in a human immunodeficiency virus-negative homosexual man.

A 35-year-old homosexual man developed a composite nodal Kaposi's sarcoma and peripheral T-cell lymphoma that were associated with a peripheral blood CD4-positive lymphocyte count of only 43/mm3. The patient subsequently developed Pneumocystis carinii pneumonitis and eventually died due to disseminated Cryptococcus neoformans. Numerous premortem tests for the presence of human immunodeficiency virus (HIV) types 1 and 2 were negative by the enzyme-linked immunosorbent assay, Western blot, viral isolation, and polymerase chain reaction techniques. Postmortem evaluations for HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-I, and HTLV-II also were negative by polymerase chain reaction, immunofluorescence assays, and viral isolation. A systemic infection by Mycoplasma fermentans, however, was documented by immunohistochemistry and polymerase chain reaction in premortem and postmortem tissues. This recently recognized human pathogen has produced systemic infections in patients with the acquired immunodeficiency syndrome (AIDS) and in previously healthy non-AIDS patients who characteristically have a fulminant flu-like illness. Additionally, M fermentans has enhanced the cytopathic effect of HIV in in vitro studies and has produced fatal wasting illnesses with terminal lymphopenia in inoculated adult silvered leaf monkeys. This report is the first description of an association between M fermentans infection and an AIDS-like illness in an HIV-negative individual. The etiology of the severe immunosuppression in this patient and the associated role of M fermentans remain to be determined by further investigations.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Combined silver Perls's stain for differential staining of ringed sideroblasts and marrow iron.

During a study of nucleolar organiser regions, a modified silver stain was found to be a sensitive marker for the iron in ringed sideroblasts, more so than Perls's stain when the marrow iron stores were low. To enhance the usefulness of the silver stain, a combined silver Perls method was developed. This stains the ringed sideroblast iron black and haemosiderin blue, thus rendering the detection of ringed sideroblasts easier even when marrow iron stores are excessive. AT the same time, it allows marrow iron content to be evaluated. The silver reagent in this combined method probably shows phosphate rather than the iron present in the abnormal mitochondria in ringed sideroblasts. This facilitates the differential staining of ringed sideroblast "iron" and haemosiderin.

Bone Marrow↗

PubMed1992

Plasmacytic differentiation in parafollicular (monocytoid) B-cell lymphoma. A study of 12 cases.

Parafollicular (or monocytoid) B-cell lymphoma (PBCL) is a recently described low grade lymphoma. The relationship of parafollicular B cells to other B lymphocytes is not known, but the authors observed plasmacytic differentiation in the initial case of PBCL. In this report 12 cases of PBCL were studied by light microscopy and immunophenotypic analysis, and plasmacytic differentiation was found in four cases. This plasmacytic differentiation and the anatomic relationship of the neoplastic cells to reactive follicular centers suggest a functional relationship between these cell types.

Aged↗

PubMed1992

T-cell-rich B-cell lymphomas. A clinicopathologic study of 19 cases.

T-cell-rich B-cell lymphomas (TCRBCLs) are recently described, unusual non-Hodgkin's lymphomas that have a diffuse morphology, a predominance of reactive T-cells, and a minority of neoplastic B-cells. The clinical and pathological features of 19 TCRBCLs, all of which demonstrated B-cell clonality, are presented. These lymphomas generally affected older patients by widespread disease and usually were nodal in origin. Treatment varied, but continuous complete remissions (eight patients) were achieved only in those receiving chemotherapy directed at intermediate-grade lymphomas. Although morphologically heterogeneous, all cases resembled peripheral T-cell lymphomas (PTCLs); several TCRBCLs also contained Reed-Sternberg-like cells. Flow cytometry or frozen-section immunoperoxidase failed to detect monotypic immunoglobulin (Ig) in eight of eight cases tested. In contrast, paraffin immunoperoxidase was very useful diagnostically, showing large L26 (CD20-associated) positive cells scattered singly or in small clusters among numerous small T-cells (UCHL1[CD45RO] positive) in all cases. Monotypic cytoplasmic Ig was present in 16 of 19 cases, one of which exhibited plasmacytic differentiation. Southern blot analysis demonstrated relatively faint Ig JH and/or JK bands, indicating a small monoclonal B-cell population in nine of 11 cases, one of which also showed a bcl-2 rearrangement. No T-cell receptor gene rearrangements were observed. These results showed that TCRBCLs may be easily confused with PTCLs or occasionally confused with Hodgkin's disease. TCRBCLs are probably heterogeneous biologically; some cases are of follicular center cell origin. These lymphomas respond to chemotherapy directed at intermediate-grade lymphomas, apparently have a better prognosis than PTCLs, and seem to represent morphological variants of different types of large B-cell lymphomas.

Adolescent↗

PubMed1992

Interleukin-4 may contribute to the abundant T-cell reaction and paucity of neoplastic B cells in T-cell-rich B-cell lymphomas.

T-cell-rich B-cell lymphomas (TCRBCLs) are diffuse lymphomas that contain a minority of large neoplastic B cells amidst a majority of non-neoplastic T cells and numerous histiocytes, an unusually pronounced reactive component not seen in most diffuse large B-cell lymphomas (DLBCLs). This reaction may be influenced by various cytokines secreted by lymphoma or reactive cells; therefore, expression of interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and IL-9 was evaluated immunohistochemically on paraffin-embedded sections of 18 TCRBCLs and was compared with that of 15 DLBCLs containing a minority of reactive T cells and to that of seven reactive lymph nodes. Moderate to intense expression of IL-4 was detected in variable numbers of tumor cells and in numerous histiocytes in 16 TCRBCLs. In contrast, intense IL-4 expression in numerous histiocytes was observed in only one of 15 DLBCLs with few T cells. In four other DLBCLs and three reactive nodes, moderate to intense staining for IL-4 was noted only in rare large transformed cells or in occasional histiocytes. Except for one IL-1 beta positive and another IL-9 positive TCRBCL, there was no marking or weak staining only with other cytokine antibodies in the neoplastic and reactive cases studied. The expression of IL-4 in most TCRBCLs, but not in other DLBCLs or in reactive nodes, suggests that this cytokine is one factor involved in the pathobiology of the abundant T-cell reaction and, perhaps, contributes to the paucity of neoplastic B cells in TCRBCLs.

B-Lymphocytes↗

PubMed1991

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma.

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (greater than 300 IU/l), 43%; and bulky (greater than 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 IV on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (less than 1000/microliters) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Adult↗

PubMed1991

Leu-22 (L60). A more sensitive marker than UCHL1 for peripheral T-cell lymphomas, particularly large-cell types.

Paraffin-embedded sections of 77 peripheral T-cell lymphomas (PTCLs) were stained with several monoclonal antibodies, including the preferential T-cell markers Leu-22 (L60[CD43]) and UCHL1 (CD45RO). The staining characteristics of L60 and UCHL1 were compared to determine the value of each in the immunophenotypic analysis of PTCLs. Lineage specificity was evaluated among 39 B-cell lymphomas and 33 cases of Hodgkin's disease (HD). L60 and/or UCHL1 stained 95% of PTCLs, whereas L60 and UCHL1 alone stained 90% and 69% of cases, respectively. L60 demonstrated significantly greater numbers of immunopositive tumor cells than UCHL1 in 37% of the PTCL cases, principally because of enhanced marking of large, neoplastic cells. UCHL1 was a better marker in only 10% of the PTCL cases. L60 stained 33% of B-cell lymphomas, usually small lymphocytic or lymphoplasmacytic types. UCHL1 stained only 8% of B-cell lymphomas, all large-cell types. L60 and UCHL1 stained Reed-Sternberg cells and variants in three cases of nodular sclerosing HD. These results suggest that both L60 and UCHL1 are useful markers of PTCLs in routinely processed tissue. L60 is a more sensitive marker of large neoplastic T-cells than UCHL1 but is less lineage-specific. These antibodies are most effective when used as part of a panel of monoclonal antibodies.

Antibodies, Monoclonal↗

PubMed1991

T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma.

A lymphoblastic malignancy presented as the lymphoid component of a recurrent invasive lymphocyte-rich thymoma that had been previously resected and treated with chemotherapy. This high grade lymphoid neoplasm concurrently involved mediastinal nodes and subsequently disseminated to pleural fluid and peripheral blood. Lymphocytes with convoluted nuclei demonstrated a T-lymphoblastic phenotype (UCHL1+, Leu-22+, TdT+) by immunohistochemical studies. T-cell lymphoblastic leukemia/lymphomas in this clinical setting have not been reported, and this case suggests that neoplastic transformation of lymphocytes may occur in longstanding refractory thymomas.

Antigens, Differentiation↗

PubMed1990

Expression of human myeloid cell nuclear differentiation antigen (MNDA) in acute leukemias.

Human myeloid cell nuclear differentiating antigen (MNDA) is a Mr 55,000 non-histone basic nuclear protein expressed in myeloid leukemia cell lines that are at late stages of differentiation (HL-60 and U937) and in normal granulocytes and monocytes, but is not present in lymphoid cells or in other human cells and tissues tested. Affinity purified monospecific polyclonal antibodies and rat monoclonal antibodies have been developed for the immunocytochemical detection of MNDA. Using these antibodies, we surveyed 21 cases of acute leukemia classified by French-American-British (FAB) Group criteria, two cases of biphenotypic acute leukemia and one case of blast crisis of chronic granulocytic leukemia for the presence of MNDA. The most intense staining reactions were present in the nuclei of two cases of acute promyelocytic (FAB M3) leukemia. MNDA was not detected in three of five cases of acute myeloblastic leukemia without maturation (FAB M1). The remaining two cases of the M1 category showed weak to moderate staining. No staining reaction was seen in acute lymphocytic leukemia (ALL), biphenotypic leukemia or the lymphoid blast crisis of chronic granulocytic leukemia. Variable staining reactions were demonstrated in the remaining cases. These data suggest that the presence of MNDA is correlated with myeloid and monocytic differentiation in acute leukemia, being strongly expressed in M3 type, often not detected in M1 leukemia and absent in ALL.

Acute Disease↗

PubMed1990

Silver stain for ringed sideroblasts. A sensitive method that differs from Perls' reaction in mechanism and clinical application.

A modified silver stain is described for the demonstration of ringed sideroblasts in bone marrow. It is more sensitive than Perls' reaction for that purpose, especially when iron stores of marrow are low or absent. Ringed sideroblasts may still be demonstrable by silver stain in cases of sideroblastic anemia without ringed sideroblasts, for which severe iron deficiency prevents detection of the abnormal sideroblasts by Perls' reaction. As iron has been reported to be present in mitochondria of ringed sideroblasts in the form of ferric phosphate, it is possible that the silver stain demonstrates the phosphate moiety and not the iron, thus explaining its greater sensitivity in iron deficiency as compared to Perls' reaction. Further study is necessary to confirm the staining mechanism, to elucidate the composition of iron deposits, and to explain the pathophysiology of sideroblastic anemia.

Anemia, Sideroblastic↗

PubMed1990

Large-cell lymphomas: clinical and prognostic features.

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.

Actuarial Analysis↗

PubMed1990

Plastic section immunohistochemistry in the diagnosis of hematopoietic and lymphoid neoplasms.

Plastic section immunohistochemistry is an important method in the multiparameter approach to the diagnosis of hematopoietic and lymphoid neoplasms. Morphologic, histochemical, and immunophenotypic data may be correlated even on small fragments of tissue by this technique. A variety of differentiation markers is detectable in plastic sections for the delineation of lymphocytic, histiocytic, and myeloid neoplasms, as well as Hodgkin's disease. Plastic section immunohistochemistry should also be useful in the diagnosis of epithelial and stromal neoplasms caused by enhanced antigen preservation in those neoplasms. For these reasons, we anticipate that the plastic section technique will have a wide variety of research and investigative applications.

Antigens, Surface↗

PubMed1990

Monomorphic lymphomas arising in patients with Hodgkin's disease. Correlation of morphologic, immunophenotypic, and molecular genetic findings in 12 cases.

Patients with Hodgkin's Disease (HD) occasionally develop monomorphic lymphomas in which mononuclear cells, usually large in size, grow in sheets, and in which there are few reacting cells or classic Reed-Sternberg (RS) cells. Twelve patients of this type were reviewed to determine the nature of the monomorphic growth. Paraffin-embedded tissue sections from the original diagnostic HD and the monomorphic growths were stained for Leu-M1 (CD15), leukocyte common antigen (LCA, CD45), pan B-cell markers LN1, LN2, and L26, and pan T-cell marker UCHL1 (CD45R) reactive in paraffin-embedded tissues. Cases were included only if the original diagnostic material had the classic histopathologic features of HD, if there was a separate monomorphic growth (in place or time), and if sufficient materials from both phases were available for study. Original diagnoses of HD included nodular sclerosing (NS; 8 cases); lymphocyte predominant (LP; 2 cases); mixed cellularity (MC; 1 case); and lymphocyte depleted (LD: 1 case) types. RS cells in the eight cases of NS HD and one case of MC HD were generally Leu-M1 and LN2 positive, and L26, LN1, UCHL1, and LCA negative. RS cells in one case of NS HD were LCA positive in addition to Leu-M1, LN1, and LN2. Two cases of NS HD showed L26 positive RS cells. Conversely, RS cells and lymphocytic-histiocytic (L and H) variants in the cases of LP HD were Leu-M1 and LN2 negative, and LCA and LN1 positive. The one case of LD HD possessed RS cells that were negative for Leu-M1, but positive for LCA, L26, LN1, and LN2. In seven cases (4 NS, 2 LP, 1 LD) the monomorphic growths possessed a B-cell phenotype (LCA, L26, and LN1 positive; Leu-M1 and UCHL1 negative). In the remaining cases (4 NS, 1 MC), the monomorphic growths were Leu-M1 positive, and displayed phenotypes similar to the RS cells of the original NS HD. Southern blot analysis was performed on the monomorphic components of five cases and showed some form of immunoglobulin gene rearrangement in each (4 cases: rearranged heavy chain-joining region gene; 1 case: rearranged Mu chain-constant region gene). Two of these cases expressed L26 and LN1 in the monomorphic phases. Despite apparent immunoglobulin gene rearrangement, one case expressed T-cell antigens Leu-4 (CD3) and Leu-1 (CD5), in addition to Leu-M1 (CD15).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1989

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗

PubMed1989

Marrow involvement in cutaneous T-cell lymphoma. A clinicopathologic study of 60 cases.

Cutaneous T-cell lymphomas (CTCLs), including Sézary syndrome, are generally assumed to spare the marrow until the disease is far advanced. The authors reviewed marrow sections from 60 patients with CTCL, looking carefully for aggregates of cerebriform cells, and found marrow involvement in 13 patients (21.7%); another 19 had abnormal lymphoid nodules that were not diagnostic of involvement, and 28 had marrows with negative results. Involved marrows had nodules or infiltrates of dysplastic cerebriform cells that were often subtle, without a significant increase in cellularity; only one case showed massive involvement. Patients with CTCL with an infiltrative component of marrow involvement had associated peripheral blood involvement (eight of eight), generalized erythroderma (six of eight), lymph node involvement (five of eight), visceral progression (five of eight), and significantly shortened median survival compared with patients with CTCL with negative marrows (11 months and 70 months, respectively; P = 0.007). In contrast, five patients with nodules of tumor in the marrow but lacking an infiltrative component did not have peripheral blood involvement; only one patient had adenopathy or visceral progression develop, and two patients have died. Significant hematologic abnormalities were generally absent. Eight of 13 patients with marrow involvement had advanced skin disease, but skin disease was limited to plaques in five patients. Eight patients had marrow involvement develop within three months of initial diagnosis. Thus, marrow involvement occurs in approximately 20% of patients with CTCL, is often present at initial diagnosis, and is associated with widespread dissemination and shortened survival time when an infiltrative component is present.

Actuarial Analysis↗

PubMed1989

Primary lymphoma of the central nervous system. A report of 20 cases and a review of the literature.

Twenty patients with primary non-Hodgkin's lymphoma of the central nervous system (CNS) were seen at Vanderbilt and its affiliated hospitals between 1974 and 1986. Histologically, the most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. However, multiple histologies were identified. Lesions most commonly involved the frontal lobes and/or deep nuclei. Positive cerebrospinal fluid cytology was rare at initial presentation. Seventeen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 5,000 cGy (range: 3,000-5,600 cGy). Seven patients have been followed for less than 12 months since diagnosis. Of the remaining patients, 7 (54%) survived at least 1 year. The extent of surgery performed, dose of radiotherapy administered, subclass of lymphoma diagnosed, or location(s) of involvement within the CNS did not influence survival. Treatment rarely caused a dramatic improvement in performance status despite objective signs of response. New treatment strategies are needed to improve the management of these tumors.

Adult↗

PubMed1989

Immunophenotypes of Reed-Sternberg cells: a study of 19 cases of Hodgkin's disease in plastic-embedded sections.

The immunophenotype of Reed-Sternberg (RS) cells in Hodgkin's disease (HD) has not been clearly defined, partly owing to difficulties in studying RS cells in cell suspensions or identifying them with certainty in frozen sections. We studied the immunophenotype of RS cells with a recently developed plastic section immunohistochemical technique on acetone-fixed tissues that affords superior morphological detail while preserving a wide variety of lymphoid differentiation antigens. Nineteen cases of HD [16 nodular sclerosing (NS), 2 mixed cellularity (MC), and 1 lymphocyte depleted (LD)] were embedded in plastic and stained for pan-B, pan-T, and various T-subset markers, as well as leukocyte common antigen (CD45), interleukin-2 (IL-2) receptor (CD25), and RS cell markers CD15 and CD30. RS cells were positive for CD45, CD15, CD30, and CD25, except for 3 cases (2 NS, 1 MC) that were CD15 negative and 2 cases (NS) that were CD45 negative. In 10 cases (NS), RS cells were positive for at least two pan-T-cell markers and CD4; pan-B cell markers were uniformly negative. RS cells in 6 cases (3 NS, 2 MC, 1 LD) were positive for at least one T-cell marker (CD2) and one B-cell marker (CD22). Two cases of NSHD showed no T- or B-cell marking. These data provide further evidence that RS cells in some cases of NSHD have T-cell phenotypes and that RS cells are not homogeneous in their immunoreactivity.

Antibodies, Monoclonal↗

PubMed1989

Response of neoplasms of B cell lineage to the proliferative effects of B cell growth factor and the phorbol ester TPA.

Little information is available regarding the role of soluble growth factors in neoplastic B cell proliferation. The authors have measured B cell growth factor (BCGF)-induced proliferation in B lymphocytes isolated from 28 patients with malignancies representing different stages of B cell differentiation. The phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate), a potent mitogen and inducer of BCGF receptor expression in normal B cells, was added in combination with BCGF to enhance the proliferative response. These results show that many neoplastic B cells are able to respond to BCGF (32%), particularly when combined with TPA (63%). The response was variable in frequency and magnitude within clinicopathologic groups; cells from patients with non-Hodgkin's lymphoma (NHL) were more refractory to stimulation than those from acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). An attenuated response to BCGF plus TPA was observed in neoplastic cells with high rates of spontaneous DNA synthesis from all histologic categories. These observations suggest that some maximally stimulated cells appear incapable of responding to additional exogenous growth stimuli. Within apparently homogeneous clinicopathologic groups, distinct subgroups of B cell neoplasms can be defined by cellular responses to BCGF. The correlation of this biologic feature with the clinical behavior of the neoplasm requires additional study.

B-Lymphocytes↗