Donald L. Sweet

Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma.

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.

Survival of patients with localized histiocytic lymphoma

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, IE, II, and IIE. Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved‐field radiotherapy. The survival rate and relapse‐free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.

Diffuse histiocytic lymphoma with sclerosis: A clinicopathologic entity frequently causing superior venacaval obstruction

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to mega‐voltage radiotherapy alone and relatively resistant to combination chemotherapy.

Acute myelogenous leukemia and thrombocythemia associated with an abnormality of chromosome No. 3

Abstract The association of thrombocythemia with acute myelogenous leukemia (AML) is unusual. A patient with markedly increased platelet counts in association with abnormal megakaryocytes was diagnosed as having AML. In addition a karyotypic abnormality involving a translocation of the long arm of a No. 3 chromosome was identified by Q-banding techniques. The translocation involved the other chromosome No. 3 [ins (3;3) (q26;q21q26)]. A specific structural rearrangement in human chromosomes in AML may be associated with abnormal megakaryocytes and increased platelets.

Non-hodgkin's lymphoma, poorly differentiated lymphocytic and mixed cell types. Results of sequential staging procedures, response to therapy, and survival of 100 patients

The results of sequential staging procedures including laparotomy, radiotherapy, and combination chemotherapy are reported for 100 patients with poorly differentiated lymphocytic (PDL) and mixed cell (MC) non‐Hodgkins lymphoma (NHL). Twelve patients were found to have localized disease, pathologic stage (PS) I or II; 88 patients had PS III or IV disease. Bone marrow biopsy showed a high incidence of involvement and advanced 34% of the patients from CS I, II, and III to PS IV. Staging laparotomy has a very limited role in the evaluation of these patients. All of 12 patients with PS I and II NHL were treated with radiotherapy; at 5 years, they had 100% survival, 80% being disease‐free. Fifteen patients with PS III disease were treated with total nodal radiotherapy (TNRT) alone and had a median disease‐free survival of 41 months. The remaining patients with PS III and IV disease were treated with chemotherapy consisting of vincristine and prednisone (V & P); cyclophosphamide, vincristine (Oncovin®), procarbazine, and prednisorte (COPP); cyclophosphamide, vincristine (Oncovin®), adriamycin, and prednisone (COPA); or “palliative therapy”, consisting of chlorambucil and prednisone. Two‐year and 4‐year survivals for patients with diffuse lymphoma were 93% and 60%, respectively; for patients with +2 nodular lymphoma, 80% and 30%; for patients with nodular lymphomas, 76–93% and 50%, respectively. Treatment with COPP showed no advantage over V and P, “palliative therapy,” or TNRT for patients with +2 nodular and nodular disease. The likelihood of cure appears most promising for patients in complete remission (CR) with diffuse lymphoma; patients in CR with nodular lymphoma show a high rate of relapse over 5 years of observation. We conclude that staging laparotomy in PDL and MC NHL is of limited value, and that the role of aggressive chemotherapy for patients with +2 nodular and nodular lymphoma needs to be redefined.

Multicentric Angiofollicular Lymph Node Hyperplasia with Peripheral Neuropathy, Pseudotumor Cerebri, IgA Dysproteinemia, and Thrombocytosis in Women: A Distinct Syndrome

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Hairy cell leukaemia: evidence for the existence of a spectrum of functional characteristics.

Functional markers of malignant cells from 14 patients with hairy cell leukaemia were evaluated during a 10 month period to assess the possible existence of sub‐types of the disease. Surface immunoglobulin on the hairy cells from the peripheral blood was studied initially, and again either after trypsinization and culture or after culture alone. Resynthesis of surface immunoglobulin occurred in all 12 patients studied; in four it was clearly monoclonal. Hairy cells from 11 patients were evaluated for their capacity to phagocytose zymosan; in five patients, 25% or more of the hairy cells demonstrated phagocytosis; in five others, less than 10%. One patient had only 13% zymosan phagocytosis initially, but when the study was repeated at a later date, 31% of the hairy cells phagocytosed. There was no phagocytosis of zymosan by malignant cells in 12 patients with a variety of other lymphoproliferative diseases. The percentage of E‐rosettes was correlated inversely with the percentage of circulating hairy cells. EAC‐rosettes were very low in three patients tested, all of whom had a high percentage of hairy cells. The number of tartrate‐resistant acid‐phosphatase‐positive cells varied from patient to patient, and within the same patient at different times. Platelet function was abnormal in six of 11 patients tested, who had a decreased, but not absent, epinephrine response. The significance of these findings in regard to the origin of the hairy cells in hairy cell leukaemia and in regard to the variable clinical course remains to be established.

Avascular Necrosis of the Femoral Head with Combination Therapy

Four patients with malignant lymphoma who were treated with multiple courses of combination chemotherapy, consisting of cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP), developed avascular necrosis of the femoral head(s). Disorders usually associated with the development of avascular necrosis were absent. The total prednisone dose received by each patient was small. Avascular necrosis of the femoral head should be considered in the differential diagnosis of bone pain in patients receiving multiple courses of combination chemotherapy.

Treatment of diffuse histiocytic lymphoma (DHL) with COMLA (cyclophosphamide, oncovin, methotrexate, leucovorin, cytosine arabinoside): a 10-year experience in a single institution.

Between March 1974 and December 1983, 83 patients with diffuse histiocytic lymphoma (DHL) were treated with COMLA (cyclophosphamide 1.5 g/m2 day 1; Oncovin (Lilly, Indianapolis) 1.4 mg/m2 days 1, 8, and 15; and cytosine arabinoside 300 mg/m2 and methotrexate 120 mg/m2 days 22, 29, 36, 43, 50, 57, 64, and 71; and leucovorin 25 mg/m2 every six hours X 4, beginning 24 hours after methotrexate). For the purpose of analysis, patients were divided into two groups. Group 1 (n = 54) included patients age 65 or under who had received no prior curative radiotherapy or chemotherapy. Group 2 (n = 29) included all patients over age 65 and patients who had received prior curative radiation therapy or prior minimal chemotherapy. The median time of follow-up for all patients was 28 months. Group 1 included 11 stage II, ten stage III, and 33 stage IV patients. Of 48 evaluable patients in this group, 21 (44%) achieved a complete remission (CR), eight (17%) achieved a partial remission (PR), and 19 (40%) showed no response (NR). Median survival of CR patients was 114+ months, PR patients, 42 months, and NR patients, 13 months. Six CR patients relapsed. The median disease-free survival of CR patients was 108+ months. Group 2 included nine stage II, seven stage III, and 13 stage IV patients. Of 24 patients evaluable for response, eight (33%) achieved a CR, six (25%) achieved a PR, and ten (42%) showed no response. The median survival of CR patients was 114+ months, that of PR patients was 17 months, and that of NR patients, 9 months. Two CR patients relapsed. The median disease-free survival of CR patients had not been reached at 102 months. The regimen was well tolerated in most patients and toxicity was acceptable. We conclude that COMLA is a well tolerated outpatient chemotherapy regimen capable of inducing durable CRs in some patients with DHL. Results achieved with COMLA, however, are inferior to those of more aggressive treatment programs; thus, the use of COMLA as first-line therapy in DHL should be limited to those patients unable to tolerate a more aggressive treatment program.

Acute leukemia following inflammatory bowel disease

Two patients are described who developed acute leukemia during a 7- to 20-year quiescent phase of inflammatory bowel disease. The possibility of an association of leukemia to the diagnostic radiation received or a susceptibility to malignancy other than adenocarcinoma in patients with inflammatory bowel disease is suggested.