NON-HODGKIN'S LYMPHOMA INVOLVING THE CENTRAL NERVOUS SYSTEM

Abstract: :In 44 out of 758 patients (5.8%) with non-Hodgkin's lymphoma presenting between 1971 and 1982, the central nervous system (CNS) was involved. Patients with a diffuse histology had a 7.6% (34/449) incidence of CNS involvement compared to 3.9% (10/257) for patients with nodular lymphoma. In 63% of patients there was evidence of progressive systemic lymphoma at the time of diagnosis of CNS disease and in 23% CNS relapse occurred in clinical remission. Bone marrow was involved in 34% of patients at diagnosis and in 52% at some time prior to the onset of CNS complications. Cerebrospinal fluid cytology was positive in 63% and an elevated protein level was found in 95% of patients. The median length of survival of the 44 patients was only 3.2 months, but patients who responded to treatment of CNS lymphoma survived significantly longer than those who showed no response or progressed on therapy. Complete response to CNS treatment was achieved in five patients, of whom none relapsed in the CNS and two are long-term disease-free survivors. CNS prophylaxis appears justified for patients with lymphoblastic lymphoma, Burkitt's tumour, and diffuse undifferentiated lymphoma, who are at high risk of developing CNS complications. Patients with diffuse histiocytic, and diffuse poorly differentiated lymphocytic, lymphoma who have bone marrow involvement may also benefit from CNS prophylaxis.     

Richter's syndrome: Diffuse histiocytic lymphoma in patients with chronic lymphocytic leukemia: A report of five cases and review of the literature

The development of diffuse “histiocytic” lymphoma in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome, occurs infrequently, but it is a distinct clinicopathologic phenomenon. In this report we describe five new cases of Richter's syndrome and summarize data on an additional 41 patients. Information from three separate series suggests a 3 to 10 per cent incidence of diffuse histiocytic lymphoma in patients with CLL. There were no features of CLL in these 46 patients in whom diffuse histiocytic lymphoma subsequently developed which would have distinguished them from patients with typical CLL in whom diffuse histiocytic lymphoma never developed. The median interval between the diagnosis of CLL and the recognition of diffuse histiocytic lymphoma in these 46 patients was 24 months (range, less than one month to 156 months). Fever (65 per cent), increasing lymphadenopathy (46 per cent), weight loss (29 per cent) and abdominal pain (26 per cent) were the clinical features which characterized the development of diffuse histiocytic lymphoma. Median durations of survival from the diagnosis of CLL and diffuse histiocytic lymphoma were 28 months and four months, respectively. Thirty-four per cent of the patients had received no treatment for CLL prior to the diagnosis of diffuse histiocytic lymphoma. Cytotoxic therapy for diffuse histiocytic lymphoma was generally unsuccessful in patients with Richter's syndrome (14 per cent complete remission rate). Clinical features of diffuse histiocytic lymphoma, which have been associated with poor response to combination chemotherapy (bulky lymph node masses, gastrointestinal or bone involvement and previous exposure to cytotoxic drugs), were common in these patients and may have contributed to the poor therapeutic response. Morphologic and immunologic studies suggest that the diffuse histiocytic lymphoma seen in patients with CLL arises as a proliferation and “dedifferentiation” of the lymphocytes of the preexisting CLL. Absolute proof that diffuse histiocytic lymphoma arises as a clonal progression of CLL cells is lacking, however, and further study of the genesis of diffuse histiocytic lymphoma in CLL is required.     

Echocardiographic identification of cardiac abnormality in scleroderma and related disorders.

Although pathologic examination may readily disclose cardiac abnormality in patients with scleroderma, clinical identification of primary heart involvement can be difficult. In order to assess left ventricular systolic function, chamber size and wall thickness, and to determine whether pericardial effusion is present, echocardiograms were obtained in 11 patients with progressive systemic sclerosis (PSS) and in 13 patients with forms of scleroderma in which visceral involvement has been considered rare or absent: three with CREST syndrome, three with morphea, three with diffuse fasciitis with eosinophilia, and four with mixed connective tissue disease. Increased left ventricular wall thickness was noted in 13 of 23 (57 per cent) patients who could be evaluated, including six (46 per cent) from subgroups other than PSS. Left atrial dimension was increased in 12 patients (52 per cent) whereas the left ventricular end-diastolic dimension was increased in only three (13 per cent). Mitral valve closure velocity, an index of left ventricular compliance, was diminished in 10 (42 per cent) patients. However, left ventricular systolic contractile performance was normal in all. Pericardial effusion was detected in five patients (21 per cent), including one patient each with morphea, mixed connective tissue disease and diffuse fasciitis. Cardiac abnormalities were evident even in patients with PSS and no renal or severe pulmonary involvement. Thus, primary cardiac involvement, characterized by left ventricular wall thickening, decreased left ventricular compliance, left atrial enlargement and pericardial effusion, may be common in patients with scleroderma. These abnormalities occur in patients with PSS as well as in those with “nonsystemic” forms of scleroderma and are readily detected by echocardiography.     

Diffuse pulmonary infiltrates in immunosuppressed patients. Prospective study of 80 cases.

Over a two year period, we studied prospectively 80 cases of diffuse pneumonia at Memorial Sloan-Kettering Cancer Center. In 72 per cent of these, the patient had leukemia or lymphoma. Diagnostic procedures consisted of extensive serologic testing for antibody to known respiratory pathogens, including the agent of Legionnaire's disease, and culturing of biopsy specimens for bacteria, viruses, mycoplasmas and fungi. Of 44 cases in which open lung biopsy was performed, a specific cause was found in 61.4 per cent: Pneumocystis carinii in 38.6 per cent, other infections in 9.1 per cent and tumor involvement in 13.7 per cent. There were nonspecific pulmonary changes in 38.6 per cent. Of the 56 cases in which biopsy, autopsy or both were performed, a specific diagnosis was made in 69.7 per cent: P. carinii infection in 37.5 per cent and other infections in 12.5 per cent. In cases in which neither biopsy nor autopsy was performed, a specific infection was diagnosed in 33 per cent; no specific diagnosis was made in the remainder. One patient in the entire group had a significant antibody titer for Legionnaire's disease. Although diagnostic in some cases, extensive serologic testing proved relatively unfruitful. Pneumocystosis was the most frequent diagnosis in this study. The cause of some cases remained obscure, even after lung biopsy.     

Central nervous system relapse in malignant lymphomas: risk factors and implications for prophylaxis

The records of 292 patients with malignant lymphoma other than Hodgkin's disease, registered in our protocols from 1967 to 1977, were reviewed to identify those with central nervous system (CNS) involvement. Thirty-one patients were encountered with this complication, an incidence of 11%. Patients with a diffuse histology had a higher frequency of CNS recurences (27/174 = 16%) in contrast to only 4/118 (3%) for those with nodular types. However, if only patients with diffuse histology in CR are considered, the frequency of CNS relapse is 13.5% (13/98). The risk factors that predict for the development of this complication were studied using multivariate analysis. Diffuse poorly differentiated lymphocytic and diffuse undifferentiated lymphomas were found to be associated with a high risk of CNS relapse. Prior chemotherapy, bone marrow involvement, age less than 35, and extranodal disease were also identified as high-risk factors. Using the information generated by a logistic regression model, patients with malignant lymphoma of diffuse type can be classified into three categories when first seen: low-risk group, intermediate, and high-risk group. CNS prophylaxis is recommended for the intermediate and high-risk group, while only close follow-up is advised for the low-risk group patients who have one adverse characteristic.     

Primary mediastinal lymphoma in adults

The incidence of primary mediastinal lymphoma in adults was investigated in 184 patients with non-Hodgkin's lymphoma. This entity was defined as disease within the mediastinum in patients who presented with symptoms due to an enlarging mediastinal mass. Of 184 patients, 17 presented with primary mediastinal lymphoma. All had a diffuse histologic pattern. The most common pathologic type was poorly differentiated lymphocytic lymphoma, diffuse (PDL-D), (11 cases). In nine of these 11 cases the patients had tumors of convoluted lymphocytes. The presentation was rapid in onset, with heart failure, pericarditis, dyspnea and superior vena caval syndrome predominating. Eleven of the 17 were clinical stage I or II, but eight of these had widespread disease on pathologic staging or rapid dissemination soon after diagnosis. In conclusion (1) primary mediastinal lymphoma is always diffuse in histology. (2) The most frequent pathologic type is PDL-D, with convoluted morphology. (3) Compression of vital intra-thoracic structures is common. (4) Although seemingly localized at presentation, this entity usually implies disseminated disease.     

Arteriosclerosis obliterans in young women

Thirty-one nondiabetic women with the onset of symptomatic peripheral vascular disease before the age of 46 years were studied to determine the risk factors important in the development of the disease and the natural history of the disease in a young population. Patients with vasculitis or embolic occlusion were excluded from analysis. All 31 women were smokers at the time of onset of symptoms, and cigarette use in general was heavy. Of the 31 patients, 20 (65 per cent) had hyperlipidemia and 14 (45 per cent) had hypertension; 16 (52 per cent) had positive family histories of atherosclerosis. Menstrual status did not appear significant as 27 (90 per cent) patients were premenopausal at the time of onset of the disease; of these, 11 (41 per cent) had used birth control pills. As is seen in older populations, the atherosclerosis involved more than one vascular bed, and 14 patients (45 per cent) had clinical evidence of cerebrovascular involvement. Five patients (16 per cent) had coronary artery disease.Angiographically, two groups were discernible: 21 patients (68 per cent) with localized disease of the aortoiliac system and normal distal vessels, and 10 patients (32 per cent) with diffuse atherosclerosis. There was no evidence that the aortoiliac tree was intrinsically smaller than normal.Twenty-five patients underwent surgery, and 22 had improved pulses during the immediate postoperative period. The mean follow-up for these 22 patients was 48 months. Surgical results depended on the location and severity of the disease. Thirteen of the 15 patients with proximal disease and normal distal vessels were markedly improved, whereas only one of seven patients with diffuse disease was similarly improved.     

American Burkitt's lymphoma: A clinicopathologic study of 30 cases: I. Clinical factors relating to prolonged survival

The presenting clinical characteristics and the results of therapy in 30 cases of American Burkitt's lymphoma are described. Five patients presented with localized disease. The abdomen was the most frequent site of involvement (19 cases). Serum lactic dehydrogenase (LDH) levels closely correlated with extent of tumor mass. Of the 22 patients treated with large doses of parenteral cyclophosphamide, complete remission was achieved in 13 (59 per cent). Of these only four have had a relapse, all within 12 months of treatment. The remainder are alive, free of disease and have not received any treatment for up to 80 months or more.The site and volume of tumor mass predicted for prolonged survival. None of the six patients with bone marrow or central nervous system involvement remained tumor-free. A complete remission was achieved in 8 of 9 patients with presenting LDH levels of less than 700 IU/ml and they have remained free of disease, whereas only 4 of 13 patients with LDH levels greater than 700 IU/ml had a complete response and 3 of these had a relapse within 12 months. In six cases, the massive tumor regression following chemotherapy was associated with serious metabolic consequences including hyperkalemia (six cases), hypocalcemia, hyperphosphatemia (one case) and lactic acidosis (one case). There were four sudden deaths in less than 48 hours after chemotherapy; two of these were attributable to hyperkalemia. In all cases there were large tumor masses and/or elevated serum LDH levels.     

Non-Hodgkin's lymphomas in leukemic phase: Clinicopathologic correlations

A leukemic phase occurred in 30 (14 percent) of 214 patients with non-Hodgkin's lymphoma. To determine the significance of peripheral blood involvement in each type of NHL, patients were subdivided according to a modified Rappaport classification. Each histologic subtype presented a homogeneous clinical picture which differed from that seen in other histologic subtypes. Of particular note was the recognition of two distinctive cytologic and clinical subtypes within the category of nodular lymphoma, poorly differentiated lymphocytic lymphoma (NPDL). In one subtype, the predominant cells had cytologic features akin to those of lymphoblasts. In these cases, although the interval to peripheral blood involvement was variable, the median leukemic survival was only two months. In contrast in conventional NPDL the median leukemic survival was 43+ months, and peripheral blood involvement did not appear to exert an independent effect on prognosis. In diffuse large cell lymphomas the median leukemic survival was 0.5 months, with peripheral blood involvement appearing as a terminal event associated with unresponsive disease in multiple sites. The recognition of adult lymphoblastic lymphoma as a clinicopathologic entity with a high risk of leukemic conversion, 100 percent in this study, is also confirmed.     

Gallium-67 scanning: Limited usefulness in staging patients with non-Hodgkin's lymphoma

The records of 122 patients with non-Hodgkin's lymphoma were reviewed, and the findings of the gallium scan analyzed. The scans of 93 patients were reread without knowledge of the previous readings. Two nuclear medicine physicians agreed with the original readings in 70 per cent of the cases and with each other in 89 per cent of the cases. When the data are analyzed case by case, 52 per cent true positive, 13 per cent false positive and 34 per cent false negative scans were found with only 17 per cent of the scans locating disease not found by routine physical examination and roentgenograms. Looking at individual sites of disease, the gallium scan yields an over-all detection of diseased sites of 18.5 per cent, with 72 per cent of all sites being correctly classified as positive or negative. The diffuse histiocytic, mixed and undifferentiated histologies were detected more accurately than all others, with mediastinal and extranodal sites being identified more frequently than any nodal site. The gallium scan revealed a site of disease which advanced the clinical stage in only one of 122 patients (upstaged). Only one of 122 patients was upstaged as a result of gallium scanning. These data suggest that gallium scanning may not be cost effective in the routine staging of patients with non-Hodgkin's lymphoma.     

Abdominal involvement at the onset of Hodgkin's disease

One hundred consecutive staging laparotomies were performed in untreated patients with Hodgkin's disease without an operative death. Abdominal involvement was documented in each of 16 patients with grossly positive lymphangiograms (clinical stage III). In patients with negative lymphangiograms, 12 of 50 (24 per cent) without symptoms (clinical stages I and IIA) and 16 of 34 (47 per cent) with symptoms (clinical stages I and IIB) were found to have abdominal disease. Of the 44 patients with abdominal involvement, in 15 disease was identified only in the spleen and celiac nodes; in 19 the spleen and paraaortic nodes were involved; and in 5 disease was present in the liver, spleen and paraaortic nodes. In only two patients was abdominal Hodgkin's disease restricted to the paraaortic nodes, but in an additional patient involvement was limited to the paraaortic and celiac nodes. One patient had disease in the liver and a common duct node, and another patient had disease in the liver, celiac and paraaortic nodes.Except for a few patients in whom the disease presented in the mediastinum or groin, or with lymphocyte predominance histology, patients with an insignificant risk of abdominal Hodgkin's disease could not be identified preoperatively. Neither site of presentation (neck versus axilla, or the right versus the left side of the neck), spleen size, alkaline phosphatase level nor histologic subtype (nodular sclerosis versus mixed cellularity) accurately predicted abdominal disease. Patients with clinical stage I or II Hodgkin's disease must either be explored, or treated for abdominal involvement; the need for exploration in patients with clinical stage III disease depends on the treatment plan.     

Clinical implications of a “nonspecific” transbronchial biopsy

The diagnostic accuracy of transbronchial biopsy via fiberoptic bronchoscope was reviewed in 127 noncritically ill patients. Biopsy results were analyzed according to whether a “specific” pathologic diagnosis of neoplasm, granuloma or pneumonia, or a “nonspecific” diagnosis of inflammation, fibrosis or normal lung was made. The clinical significance of a “nonspecific” biopsy specimen was evaluated by clinical follow-up of at least 12 months (mean 15 months) and by grouping patients according to the type of abnormality found on chest roentgenography.Clinical follow-up was available in 119 of these patients. The over-all “specific” diagnostic yield for biopsy with secretions was 49 per cent, with transbronchial biopsy being the sole means of specific diagnosis in 14 per cent of the patients with a peripheral mass lesion, in 18 per cent of the patients with localized infiltrative processes and in 52 per cent of the patients with diffuse infiltrative processes. In 64 (52 per cent) patients both biopsy specimens and secretions were diagnostically nonspecific. In 16 (77 per cent) patients with peripheral mass lesions but nonspecific biopsy findings and secretions, neoplasm was diagnosed by more invasive procedures. However, 22 (91 per cent) patients with localized and 12 (75 per cent) patients with diffuse infiltrative processes had benign clinical follow-up suggesting that open lung biopsy in such patients should be reserved for patients with obvious clinical or roentgenographic evidence of deterioration.     

The prognostic and therapeutic implications of DNA:anti-DNA immune complexes in systemic lupus erythematosus (SLE).

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.     

Clinical usefulness of 67gallium scanning in the malignant lymphomas.

To determine the clinical usefulness of 67 gallium (Ga) scanning in the evaluation of patients with lymphomas, we reviewed 142 total body Ga scans performed on 44 patients with Hodgkin's disease and 53 patients with non-Hodgkin's lymphoma. Fifty-two per cent (123 of 236) of known disease sites were detected on scan. The false-positive rate was less than 5 per cent. The accuracy of detecting lymphoma varied in individual anatomic areas from 33 per cent in the axilla to 73 per cent in the thorax. In eight patients with bone involvement, all bone lesions were detected on scan. The size of the lesion appeared to influence accuracy, since tumors greater than 3 cm in diameter were more often positive.     

Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience

CLM developed in 60 of 526 patients (11%) with SCLC seen at the NCI between August 1969 and June 1980. Life table analysis revealed an overall 25% risk of CLM at 3 years. CLM was diagnosed during all phases of the patients' clinical course, but the majority (83%) were cases diagnosed at the time of progressive systemic disease. Univariate log rank analysis indicated that pretreatment factors associated with the development of CLM included: involvement of the brain, spinal cord, bone marrow, liver or bone; extensive disease; and male sex. Patients who did not obtain a complete response to systemic therapy were at greater risk of developing CLM than complete responders. Multivariate analysis of these factors indicated that liver metastases were most strongly associated with the time to development of CLM, followed in order of importance by bone and CNS metastases. Patients usually presented with signs and symptoms reflecting involvement of multiple areas of the neuraxis including the cerebrum, cranial nerves and spinal cord; 51 of the 60 patients had intracerebral metastases and 27 had spinal cord lesions during their clinical course. Autopsy features including focal or diffuse involvement of the leptomeninges with infiltration of the Virchow-Robin spaces were similar to meningeal lymphoma and leukemia, except that CLM was rarely the sole manifestation of CNS tumor. Median survival following the diagnosis of CLM was 7 weeks. However, most deaths were attributed to systemic disease, and treatment with intrathecal chemotherapy and irradiation often provided palliation. With the increased awareness of this complication, an antemortem diagnosis increased from 39% prior to 1977, to 88% of patients after 1977.     

Characterization of malignant lymphomas in leukemic phase by multiple differentiation markers of mononuclear cells. Correlations with clinical features and conventional morphology.

Peripheral blood and bone marrow cells of 38 patients with malignant lymphoma in the leukemic phase were defined by multiple immunologic markers and determination of the enzyme terminal deoxynucleotidyl transferase (TdT). Despite shared B cell markers (surface immunoglobulins, binding of aggregated immunoglobulin G [IgG]) distinctions could be made between the cells of patients with chronic lymphocytic leukemia (CLL) and those of patients with other B-lymphoproliferative disorders on the basis of morphology, intensity of surface immunofluorescence and number of mouse rosette-forming cells (MRFC). In 15 patients with CLL, the mean value for MRFC was 47.5 per cent, differing significantly (p < 0.001) from the value found in 10 patients with non-CLL B-cell leukemic lymphomas (7.5 per cent) and in normal control subjects (4 per cent ± 3/mean ± 1 SD). Of 11 patients with leukemic diffuse poorly differentiated lymphocytic lymphoma (DPDL), four had cells that formed spontaneous rosettes with sheep erythrocytes (T cells), and seven had a predominance of null cells. TdT activity was present in six of six patients studied, including three patients each with the null and T cell proliferations. This group of 11 patients with leukemic DPDL was characterized clinically by prominent mediastinal involvement in 10, a median age of 29 years and a median survival of 12 months. Malignant cells of two patients with leukemic diffuse histiocytic lymphoma seemed to be of B cell origin, as they were characterized by monoclonal surface immunoglobulin M (IgM) of kappa light chain type. Leukemic cells in the remaining two patients were characterized by a prominent Fc receptor, which might be considered evidence of a monocytic disorder. These data further support the usefulness of cell marker analysis in delineating the heterogeneity of cellular types involved in leukemic and lymphomatous disorders, and suggest its eventual clinical usefulness in the diagnosis and prognosis of these disorders.     

Central nervous system involvement in patients with mantle cell lymphoma

 In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. Survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor. Received: July 30, 1998 / Accepted: November 12, 1998     

The cardiovascular manifestations of the hypereosinophilic syndrome. Prospective study of 26 patients, with review of the literature.

The major cause of morbidity and mortality in patients with the hypereosinophilic syndrome is cardiac dysfunction. A review of 65 cases from the literature (historic series) revealed the following cardiovascular manifestations to be most common: dyspnea (60 per cent), signs of congestive heart failure (75 per cent), murmur of mitral regurgitation (49 per cent), cardiomegaly (37 per cent), T wave inversions on electrocardiogram (37 per cent) and pathologic findings of endocardial fibrosis, myocardial inflammation and mural thrombus formation (57 per cent). We have prospectively followed 26 patients with the hypereosinophilic syndrome for up to nine years (average follow-up prospectively was 3.3 years, retrospectively 5.7 years). Common cardiac findings in our 26 patients were dyspnea (42 per cent), chest pain (27 per cent), signs of congestive heart failure (38 per cent), murmur of mitral regurgitation (42 per cent), cardiomegaly (35 per cent) and T wave inversions (35 per cent). Thus, these patients demonstrated cardiovascular manifestations similar to those in the historic series, although the literature review showed a higher incidence of overt congestive heart failure.Of 22 patients having echocardiograms, 55 per cent demonstrated some clinical, roentgenographic or electrocardiographic evidence of cardiac involvement, but 82 per cent had echocardiographic abnormalities. This suggests that the echocardiogram is a sensitive and perhaps early indicator of cardiac involvement in this disease. Common echocardiographic findings included increased left ventricular wall thickness (68 per cent), left ventricular mass (73 per cent) and left atrial size (37 per cent). Prospective echocardiographic follow-up of 18 patients (for up to four and a half years) revealed that seven of eight untreated or inadequately treated patients had increases in left ventricular wall thickness, whereas all 10 adequately treated patients had decreases (eight of 10) or no change (two of 10) in left ventricular wall thickness. This suggests that adequate antihypereosinophilic therapy (with prednisone and/or hydroxyurea) may stabilize and, in some cases, reverse the cardiac manifestations of the hypereosinophilic syndrome.In previous studies, congestive heart failure due to eosinophilic cardiomyopathy has been reported to be very resistant to therapy. In our patients with congestive heart failure, treatment has been almost invariably effective when digitalis and diuretics were combined with adequate antihypereosinophilic therapy.     

Bone involvement in young patients with non-Hodgkin's lymphoma: efficacy of chemotherapy without local radiotherapy

Of 95 young non-Hodgkin's lymphoma patients entered consecutively on the National Cancer Institute (NCI) Protocol 7704, 26 (27.4%) had involvement of one or more bones. The mean age of these 26 patients was 16.6 years, and the male to female ratio was 3.3:1. Tumor histology included undifferentiated Burkitt's lymphoma in 12, undifferentiated non-Burkitt's lymphoma in two, undifferentiated, unspecified lymphoma in one, diffuse large cell lymphoma in three, and lymphoblastic lymphoma in eight patients. Most had extensive disease; two patients had isolated bone lesions, one had lesions of two bones without involvement of other tissues, and 23 had either multiple bone lesions or single bone lesions with involvement of other tissues. Eight of the 26 patients had bone marrow involvement. Of a subgroup of 12 patients with jaw disease, 11 had undifferentiated lymphoma and one had diffuse large cell lymphoma. Only one had primary a jaw tumor, with two quadrants of the jaw involved. All 26 patients were treated with chemotherapy; only two received radiotherapy initially for bone lesions. Predicted survival of the 26 patients at 5 years is 53.2%. The 12 patients who remain disease free have a mean survival of 62.1 months (range, 22 to 100 months). Our results call into question the role of radiotherapy in the treatment of bone lesions in non-Hodgkin's lymphoma.     

Clinical and hemodynamic aspects of single vessel coronary artery disease

Two-hundred consecutive patients with arteriosclerotic heart disease underwent complete clinical and hemodynamic evaluation. Fifty-two patients (26 per cent) had significant single vessel coronary artery disease and were compared to 148 patients with more extensive coronary artery disease and to a group of 14 normal patients. The single vessel disease group, when compared to the diffuse disease group, was characterized by a shorter duration of angina pectoris, lower frequency of a history of congestive heart failure or cardiomegaly, and a lower frequency of electrocardiographic (ECG) evidence of a transmural myocardial infarction. The combination of angina pectoris for three or more years with cardiomegaly was the only factor which completely separated the two coronary disease groups. Cardiomegaly, when present in single vessel involvement, was always due to left anterior descending (LAD) disease, together with an anterior infarction on ECG and left ventricular asynergy. The single vessel disease group included 32 patients with LAD disease, 17 with RCA, and 3 with circumflex artery involvement. Resting hemodynamics in these 52 patients (other than a higher left ventricular end-diastolic pressure and wall stress) were not significantly different from hemodynamics in a normal group. Patients with diffuse disease were characterized by many hemodynamic alterations and by left ventricular (LV) asynergy, when compared to the single vessel disease or normal groups. The diffuse disease group had a lower ejection fraction (EF) and an increased frequency of LV asynergy and coronary collateral circulation than did the LAD group. In the single vessel disease group LV asynergy did not correlate with the ECG. LV synergy, however, was not found in any patient in the LAD group with abnormal Q waves on ECG. The single vessel disease group included only five patients with increased end-diastolic volume (EDV) and all had LAD involvement, increased LV end-diastolic pressure, and decreased EF. The remaining 47 patients with normal LV-EDV revealed that the LAD group had abnormal pressure-volume relationships, indicating a decreased compliance of the left ventricle.