High-grade Malignant Lymphoma Research Articles

Zum Auftreten epithelialer Neubildungen im Kopf-Hals-Bereich bei Non-Hodgkin-Lymphomen

There is an increased risk of malignancy in patients with genetically determined or acquired immunosuppression. The authors report a case of a 70-year-old patient with a lymphoplasmocytic immunocytoma who developed 19 squamous-cell carcinomas (SCC) and nine basal-cell carcinomas (BCC) over a three-year period. This was the reason to review 100 cases of malignant lymphomas for evidence of additional malignancies. Of these patients, 15% had one or more SCC or BCC in the head and neck area. The age range was 59 to 79 years (mean, 71.7 years) and the male:female ratio 11:4. One or more SCC arose in 93% of these patients, 36% developed an additional one or more BCC, and BCC alone occurred in 7%. The usual ratio of BCC:SCC is 10:1; in the authors' patients, by contrast, this ratio was 6:14. In 12 cases, SCC and BCC were located on the skin. The remaining cases of SCC developed in the oral mucosa, the tonsils and the hypopharynx. In 13 cases, low-grade malignant lymphomas were found and in two cases high-grade malignant lymphomas were found. The SCC were clinically aggressive. Thirty-six percent of the patients had recurrent lesions, 43% multiple neoplasms, and 50% metastases. Histologically, the SCC showed moderate to poor differentiation, a high degree of cell polymorphism and mitotic activity, and deep tissue infiltration. There are several explanations for the increased incidence of neoplasms in patients with immunodeficiency disorders. The surveillance function of the immune system may be impaired due to the disease itself or due to the treatment for immunosuppression. Immunosuppressive and cytotoxic agents are potential carcinogens.(ABSTRACT TRUNCATED AT 250 WORDS)

M-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen

A prospective study was performed to evaluate the feasibility of full dose chemotherapy given on schedule in elderly patients with unfavourable non-Hodgkin's lymphoma, stage IE, III and IV. Using a combination regimen of six courses of cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) given every 4 weeks, no serious toxicity was encountered in a group of 30 consecutive patients with a mean age of 70.4 years. A 60% complete response rate was observed and a total response rate of 90%. The disease-free survival of complete responders was 50% at 1 year. The overall survival was also 50% at 1 year. In 148 courses of CNOP only two serious infectious episodes were noted, i.e. one herpes zoster infection and one case of bronchopneumonia. Asymptomatic transient thrombocytopenia and granulocytopenia were commonly observed. Nadirs of white blood cells were WHO grade 1, 2, 3 and 4 in six, five, twelve and two patients respectively and nadirs of thrombocytopenia were WHO grade 0 and 1 (22 patients) or 2 (three patients). Based on low white blood cell counts, a delay of 1 week before administration of the next course of CNOP was necessary in 7% of the courses. No dose reductions were applied. Toxicity other than transient granulocytopenia was minor and consisted of alopecia and nausea. WHO grade 0-2. CNOP related toxicity was never a reason to stop treatment. It is concluded that CNOP chemotherapy without initial dose reduction in elderly patients with intermediate and high grade malignant non-Hodgkin's lymphoma is feasible and that no major toxicity is observed.

Low Grade Malignant Non-Hodgkin's Lymphomas and Peripheral Pleomorphic T-Cell Lymphomas in Childhood - A BFM Study Group Report

Non-Hodgkin's lymphomas (NHL) are classified as low or high grade malignant lymphomas of either B or T cell origin. Cells of low grade malignant NHL (LG-NHL) of B cell type represent either follicular or postfollicular, cells of LG-NHL of T cell type postthymic maturation stages in the lymphoid differentiation pathway. LG-NHL often fail to undergo long-term complete remission or cure in adults, no matter what type of conventional therapy is applied. In three pediatric therapy studies frequency and probability of continuous complete remission (pCCR) were studied for LG-NHL and peripheral pleomorphic T-cell lymphomas (PTCL). Of 432 evaluated patients only six children (1.4%) were qualified as LG-NHL. LG-NHL of T cell type were diagnosed in three children (one T-zone lymphoma, two PTCL of small cell type), LG-NHL of B cell type in another three cases. Two children presented with nodular type of centroblastic/centrocytic lymphoma (CB/CC), one with lymphoplasmocytoid type of immunocytoma (IC). In addition to the two patients with low grade malignant PTCL, there have been also four children with high grade malignant PTCL. The analysis showed that there was not significant difference for event free survival of children with LG-NHL and HG-NHL, respectively (pCCR: 0.63 and 0.82, p = 0.29). In contrast, when comparing high and low grade PTCL versus all other types of childhood NHL (non-PTCL), a significant difference seems to exist (pCCR for PTCL: 0.44, for non-PTCL: 0.83; p = 0.02). However, for further concisive conclusions more patients are needed for evaluation.

Lymphoplasmacytic/Lymphoplasmacytoid Immunocytoma with a High Content of Epithelioid Cells

Fifty-four lymph node biopsy specimens from 36 patients with lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells (LPICep) were studied by light microscopy using conventional histologic and immunohistochemical techniques. Three other patients with extranodal involvement only were also included in the study. Of a total of 39 patients, 31 had the polymorphic subtype, six the lymphoplasmacytoid subtype, and two the lymphoplasmacytic subtype. Cellular composition and histologic structure are described in detail as a basis for discriminating LPICep from similar lymphomas with a high content of epithelioid cells, especially from lymphoepithelioid cell lymphoma (Lennert's lymphoma), angioimmunoblastic peripheral T-cell lymphoma with a high content of epithelioid cells, and Hodgkin's disease, mixed cellularity type with a high content of epithelioid cells. In 10 patients (26%) LPICep developed into a high-grade malignant lymphoma of B-immunoblastic type. Forty-seven biopsy specimens were studied with the peroxidase-antiperoxidase method to detect intracytoplasmic immunoglobulin. Plasma cells and plasma cell precursors revealed a monotypic immunoglobulin pattern in all specimens. In 25 biopsy specimens in which giant cells resembling Sternberg-Reed and Hodgkin's cells were found, these cells were CD15 negative. A comparison of the main clinical and laboratory data in these four lymphomas with a high content of epithelioid cells revealed both similarities and differences.

Acute myeloid leukemia: Immunohistologic findings in paraffin-embedded bone marrow biopsy specimens

Immunohistochemical investigations were performed on decalcified, paraffin-embedded iliac crest trephine biopsy specimens from 30 cases of acute myeloid leukemia (AML, as defined by the FAB classification) with antibodies against B cells (L26, 4KB5, MB1, Ki-B3), T cells (UCHL1, MT1), myeloid/histiocytic cells (anti-neutrophil elastase, MAC387, anti-S-100 protein, anti-α1-antichymotrypsin, DAKO-M1), natural killer/killer cells (anti-Leu-7), and megakaryocytes (anti-factor VIII-related antigen). (1) The blast cells of all the cases reacted with from at least two to at most eight different antibodies. Each antibody reacted with blast cells in a minimum of two (maximum 30) cases. (2) MT1, Ki-B3, anti-α1-antichymotrypsin anti-neutrophil elastase, anti-S-100 protein, and MAC387 stained blast cells in more than 50% of the cases; MB1, L26, UCHL1, 4KB5, and DAKO-M1 in 20% to 50% of the cases; and anti-Leu-7 and anti-factor VIII-related antigen in less than 20% of the cases. (3) In the majority of cases many T lymphocytes, a small-to-moderate number of B lymphocytes, and a few Leu-7-positive lymphoid cells were intermingled with the blast cells. In some cases, especially where only a minor proportion of the blast cells was immunostained, it was nearly impossible to distinguish the lymphocytes of the tumor's stromal reaction from small blast cells. Thus, AML exhibits a heterogeneous immunophenotype in trephine biopsy specimens. Immunohistologic diagnosis of this disease in such specimens may be extremely difficult. Since staining of the blast cells with one or more of the antibodies generally used to define B cells, T cells, or their neoplastic derivatives is not uncommon, misinterpretation as non-Hodgkin's lymphoma of high-grade malignancy could easily occur. These findings also suggest that mixed-type (hybrid) acute leukemias with coexpression of myeloid and lymphoid cell markers could be more common than generally realized.

A case of primary osseous malignant immunoblastic B‐cell lymphoma with intracytoplasmic mu lambda immunoglobulin inclusions

Primary malignant lymphoma of bone, so-called Parker-Jackson reticulosarcoma, is a rare form of extranodal lymphoma with a relatively good prognosis. It often corresponds to B-cell lymphoma of high-grade malignancy. We report a case of mu lambda immunoblastic lymphoma showing two distinctive features: an abundant reactive T-lymphocytic population and unusual intra-cytoplasmic inclusions. These inclusions were PAS positive and consisted of monotypic mu lambda immunoglobulin localized in peculiar aggregates of rough endoplasmic reticulum. Their morphological appearances resembled the well-documented inclusions described in some varieties of non-Hodgkin's lymphoma.

Long-term follow-up of CHOP-treated non-Hodgkin lymphoma of high-grade malignancy

The long-term outcome of 116 NHL patients (38 CB, 33 IB, 24 LB, 11 high-grade unclassified, 9 PTCL, 1 Ki-1 lymphoma - see list of abbreviations) treated with an age-adjusted CHOP regimen from 1980-85 was evaluated. The median age was 64 years. Of these patients 28% had significant comorbidity. CB patients had the best outcome; the median survival was not reached after 110 months. However, the differences in survival of all histological entities are not significant (P = 0.08). Fifty-six percent of the patients had clinical stages I-II. The CR rate of all 116 patients was 47%. After a median follow-up of 58 months, 30% of the patients are alive and disease-free. Of 14 relapses 11 occurred within 2 years. The median time period before relapse was 9 months. Salvage therapy failed, as none of the IB and LB patients achieved CR. Five CB patients had CR with second-line therapy, four had PR after induction therapy, one patient relapsed after 30 months. Of the CR patients 15% developed second or third neoplasms. Only one instance of acute myeloblastic leukemia was observed. These results indicate that age-adjusted CHOP is a well-tolerated therapy.

Phase III Trial of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (Chop) Versus Cisplatin, Etoposide, Bleomycin and Prednisone (CisEBP) for the Treatment of Advanced Non-Hodgkin's Lymphoma of High Grade Malignancy

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CisEBP (cisplatin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocytopenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.

Ferritin im Serum – Ein ‘Tumormarker’ bei malignen Lymphomen?

Serum ferritin concentration as a tumor associated marker was investigated in 535 patients with malignant lymphomas. The study included 207 patients with Hodgkin lymphomas, 196 patients with low grade malignant Non Hodgkin lymphomas and 132 patients with high grade malignant Non Hodgkin lymphomas of different tumor stages. Increased serum ferritin concentrations were found in 54% of the unselected patients. In particular, serum ferritin concentration was elevated in 12.3% of patients with stage I, in 33.8% of patients with stage II, in 72.2% of patients with stage III and in 94% of patients with stage IV. The serum ferritin levels correlated with the tumor mass. There was no difference between Hodgkin lymphomas and Non Hodgkin lymphomas. In patients with concomittant hepatocellular disease or during chemotherapy inadequate high serum ferritin concentrations were found, which did not correlate with tumor mass. In patients with primary bone marrow infiltration by some low grade malignant Non Hodgkin lymphomas serum ferritin levels correlated better with the tumor stages according to Rai than with the Ann-Arbor-classification. The serum ferritin concentration followed closely the activity of the disease: Increased pretreatment serum ferritin levels normalized completely, when patients achieved complete remission. In contrast, in patients with tumor relapse or tumor progression serum ferritin levels increased again. The data suggest that the serum ferritin concentration can be used for follow-up of patients with malignant lymphomas. Because of its limited specifity and low sensitivity it cannot be used as a screening test. Nevertheless, it is a helpful additional parameter for the control of the activity of the disease.

MACOP-B Chemotherapy for the treatment of high grade and intermediate grade Non Hodgkin's lymphoma

Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group with relapsed disease 14% had PR and 14% had progressive disease (PD). At a medium follow-up of 12 months (range 1 month to 33 months), 74% of patients with de novo NHL continued to be in CR whereas the continuous CR rate in patients with relapsed disease was 35%. Overall survival after 30 months of observation for the patient group with de novo NHL was 75% and 40% for patients with relapsed NHL. The mean duration for completion of the projected 12 chemotherapy cycles, given in weekly intervals, was 12.9 and 13.5 weeks in upfront or salvage therapy, respectively. With low incidence of major toxicities, application of drugs on an outpatient basis, and high efficacy, MACOP-B shows substantial advantages for therapy of de novo and relapsed NHL.

Interferon alpha in der Therapie der Non-Hodgkin-Lymphome

Interferon alpha is a new therapeutic option in malignant Non-Hodgkin's lymphomas. Favourable results have been achieved in low-grade malignant histologies. Objective responses have been reported in 39% of patients with nodular histology (mostly centrocytic-centroblastic according to the Kiel classification), most of them being partial remissions. Clinical studies suggest a dose-response relationship. Interferon alpha has also been combined with alkylating agents. The toxicity of the combination is subjectively and objectively well tolerable. Though combinations are very active with high response rates, an improvement of survival has not been shown. In other studies interferon alpha has been administered for maintenance after induction chemotherapy. Responses have been noted in only 16% of patients with advanced chronic lymphocytic leukemia. In early stages (mostly Binet stage A) the disease is more sensitive with a response rate of 73%. As the prognosis of these patients is very good, the relevance of the therapeutic response is not clear. The results of interferon alpha in cutaneous T-cell lymphoma and mycosis fungoides are controversial. Based on pooled published data, the overall response rate is 44%. High-grade malignant non-Hodgkin's lymphomas have been treated with high doses of interferon alpha. The overall remission-rate is 14%. In most cases, remissions have been short.

Computer aided cytometry in high grade malignant non-Hodgkin's lymphomas and tonsils.

The aim of the study is to establish quantitative cytological criteria for reliable diagnoses in high grade malignant non-Hodgkin's lymphomas (NHL). For this purpose Pappenheim-stained cytologic imprints from 15 cases of high grade malignant NHL and ten cases of chronic tonsillitis have been analysed using a TV-microscope system, high resolution color scanning (13.3 pixel/microns), and image processing on a computer. The highly reliable computer-extracted cell features can be used to discriminate the different cell types of malignant NHL. Because of a considerable overlap, no feature on its own is sufficient to discriminate all the different cells. Only multivariate analysis of a suitable combination of features allows reliable discrimination. The results show that the different cells defined by subjective morphological criteria in the Kiel-classification of malignant NHL also form distinctive subpopulations with regard to their objective mathematical cell features and show distinctive differences when compared with their benign counterparts derived from reactive lymphatic tissue.

Nodular paragranuloma can transform into high-grade malignant lymphoma of B type.

A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B-type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B-cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed.

Large cell anaplastic lymphoma of the skin.

Large cell anaplastic lymphoma (LCAL) is a recently described entity recognized by its constant expression of the CD30 antigen and by its morphology. LCAL is classified as high grade malignant lymphoma. We report 10 patients with LCAL of the skin, three with primary LCAL and others in which it developed with cutaneous T-cell lymphoma, mainly mycosis fungoides. The immunophenotype in all but one of these cases, was that of activated T cells.

Production of growth factors by malignant lymphoma cell lines

Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi- solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA- LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

Production of Growth Factors by Malignant Lymphoma Cell Lines

Fourteen Epstein-Barr virus (EBV)-negative cell lines were raised from bone marrow (BM), peripheral blood (PB), or lymph node samples of patients with intermediate- or high-grade malignant lymphoma. The cell lines were propagated in liquid suspension culture. They contain clonogenic progenitors capable of forming lymphoma colonies in semi-solid culture medium. Cells of these lines were used to examine the growth factor requirements of their clonogenic progenitors and to assess their ability to produce their own growth factors. Two of the cell lines (OCI-Ly9 and OCI-Ly13.1) required addition of exogenous factors for colony growth. These factors were routinely provided by media conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM). Three lines formed some and nine lines gave rise to optimal numbers of colonies without addition of growth factors. Eight of these factor-independent lines were able to function as feeder cells and promoted colony formation by both factor-dependent lines. Cell lines that displayed feeder cell function released activities into supernatants able to replace their cellular source. Some of these endogenously produced growth-promoting activities could be replaced by known hematopoietic growth factors. Both factor-dependent cell lines were cultured with recombinant IL-1 alpha, IL-2, IL-3, IL-6, and GM colony-stimulating factor (CSF) and semipurified B-cell growth factor (BCGF) interleukin-4 (IL-4). A heterogeneous response pattern was observed. Both lines formed colonies with IL-4. The colonies were comparable in frequency and size with colonies observed with (PHA-LCM). OCI-Ly9 responded to IL-6 but showed no growth with IL-2. In contrast, the TAC-positive line OCI-Ly13.1 gave rise to colonies with IL-2 while remaining unresponsive to IL-6. A moderate number of colonies was observed when cells of this line were cultured with GM-CSF. Colony formation of both lines was uninfluenced by IL1 alpha or IL-3.

LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma.

From July 1984 to September 1987, 737 patients with aggressive malignant lymphoma (ML) were treated by an intensive regimen (LNH-84) comprising three or four courses of doxorubicin, 75 mg/m2; cyclophosphamide, 1,200 mg/m2; vindesine, 2 mg/m2 x 2; bleomycin, 10 mg x 2; and prednisolone, 60 mg/m2 x 5 (ACVB), consolidation with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytarabine, and a randomized late intensification with two courses of cytarabine, cyclophosphamide, teniposide, bleomycin, and prednisone (AraCVmB). Four hundred forty-two patients had intermediate-grade ML, 221 highgrade ML, and 74 unclassified ML. Most of the patients had advanced disease: stage IIE (23%), III (13%), or IV (47%); 38% disseminated nodes; 38% two or more extranodal sites; and 41% a tumoral mass greater than 10 cm. Five hundred fifty-three patients (75%) went into complete remission (CR), 63 (9%) into partial remission, 62 (8%) failed to respond, and 59 (8%) died during ACVB courses, 17 of them from progression of the disease. With a median follow-up of 23 months, the estimated 2-year overall survival time to failure (TTF), and time to relapse (TTR) survival are 67%, 56%, and 67%, respectively. Patients receiving a late intensification had the same relapse rate as the other patients. A persistent fibronecrotic mass was found in 150 patients (20%) and did not influence the relapse rate. Toxicity was mainly neutropenia and infection during the ACVB courses, with 40 patients (5%) dying from septic complications while responding to treatment. Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L, 58% fever (6% grade 4), and 49% a documented infection (8% grade 4). These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML.

Bone marrow and blood involvement by non‐Hodgkin's lymphoma: A study of clinicopathologic correlations and prognostic significance in relationship to the Working Formulation

In a series of 172 patients with non-Hodgkin's lymphoma (NHL) classified according to the Working Formulation (WF) the overall incidence of bone marrow infiltration (BM+) at diagnosis was 39%: 59% for low-grade (LGML), 30% for intermediate-grade (IGML), and 25% for high-grade malignant lymphomas (HGML). The features most significantly correlated with the presence of BM+ were a low grade of histological malignancy, the degree of splenomegaly and high values of LDH, while those correlated with the extent of BM+ were a non-focal pattern of BM disease, the presence of blood involvement at diagnosis, and the degree of BM fibrosis. Blood involvement was detected at diagnosis in 13% of patients, and a further 16% developed a leukemic phase during the course of the disease. Blood involvement correlated significantly with splenomegaly, bulky disease, advanced clinical stage, and extent of BM+. The presence of BM infiltration 'per se' at diagnosis did not significantly affect prognosis. However, the extent of BM disease was correlated with a poorer outcome in IGML and HGML patients. Regarding peripheral blood involvement, in LGML patients only late leukemic conversions were significantly associated with a worse prognosis. In patients with IGML and HGML, either initial or subsequent blood involvement was correlated with significantly poorer outcome.

Cytogenetic characterization of a high-grade murine B-cell lymphoma

The chromosomal pattern of a high-grade malignant B-cell lymphoma that arose spontaneously in a C57BL mouse is described. A considerable amount of structural chromosomal abnormalities was found in the lymphoma cells. These abnormalities are discussed in view of their possible role for oncogenesis, infiltration, and tissue distribution. The chromosomal findings of this lymphoma are compared with the few that have been described previously.