Robert E. Rydell

Refined chromosome study helps define prognostic subgroups in most patients with primary myelodysplastic syndrome and acute myelogenous leukaemia

Based on a 6·1/2‐year study of 284 consecutive adult patients with primary myelodysplastic syndrome (MDS) and and acute myelogenous leukaemia (AML), we have found that refined chromosome analysis can be used as an independent prognostic indicator in the great majority of patients with MDS and AML. In MDS, the FAB subtype was also found to have prognostic value and this was enhanced when the chromosomal findings were taken into consideration. In AML, the age of the patient correlated more closely with the chromosomal changes in predicting prognosis in most patients than did the FAB classification.

Multiple pulmonary arteriovenous fistulas in juvenile cirrhosis

Abstract Clinical and pathologic findings in a case of juvenile cirrhosis associated with cyanosis, clubbing of the digits, greatly elevated cardiac output and a long bruit are presented. Although careful examination of the lungs at necropsy, both grossly and microscopically, failed to reveal any significant pathology, injection of a plastic solution into the pulmonary vessels revealed the presence of numerous abnormal vascular channels connecting the pulmonary arteries and veins. Thus the presence of multiple arteriovenous fistulas in the lungs, suspected and sought for during the patients life, was finally confirmed. Pulmonary arteriovenous fistulas of the classical type may be multiple. The findings in the present case suggest an entirely different process. A review of the literature has failed to reveal similar reported cases, probably because injection studies of the pulmonary vascular tree have not been performed in instances of juvenile cirrhosis associated with cyanosis and clubbing.

Richter's syndrome in chronic lymphocytic leukemia

Over an 18‐year period a distinctive large cell lymphoreticular neoplasm (Richters transformation) developed in 9 patients with chronic lymphocytic leukemia. Clinical findings at the onset of Richters transformation were remarkably uniform and consisted of the abrupt onset of fever, marked asymmetric lymphadenopathy with the formation of masses, splenomegaly, and hepatomegaly. All patients underwent rapid clinical deterioration followed by death within six and a half months. Earliest infiltrates of large lymphoreticular cells were identified in the lymph nodes in 3 of 4 patients and the bone marrow in 3 of 9 patients, while no patient had peripheral blood involvement. Autopsy examinations revealed extensive infiltrates of large lymphoreticular cells, predominantly in bone marrow, lymph nodes, liver, spleen, but also in kidney, lung, and gastrointestinal tract. In each case, these large lymphoblast‐like and pleomorphic lymphoreticular cells were admixed with mature‐appearing lymphocytes and intermediate forms (prolymphocytes). Electron microscopic and immunoperoxidase studies provided additional evidence that this highly aggressive lymphoreticular neoplasm represents a transformation or dedifferentiation of chronic lymphocytic leukemia. Cancer 46:118–134, 1980.

Chronic myelodysplastic syndrome: short survival with or without evolution to acute leukaemia

Summary. The myelodysplastic syndromes represent a prognostically diverse group of disorders. Their study has recently been facilitated by the classification proposed by the French‐American‐British (FAB) Cooperative Group. Using this scheme it is now possible to define more precisely their natural history and clinical relationship to acute leukaemia. Using the longitudinal case control technique, we reviewed the clinical data and morphology of 69 patients (all elderly males) with chronic irreversible haematological cytopenia and dysplasia. Applying FAB criteria we found: refractory anaemia (RA) in 43%; sideroblastic anaemia (RA‐S) in 33%; refractory anaemia with excess blasts (RAEB) in 13%; RAEB in transformation (RAEB‐T) in 9% and chronic myelomonocytic leukaemia (CMML) in 1%. The median survival for the entire group was 27 months (RA, 52; RA‐S, 29; RAEB, 12; RAEB‐T 11; and CMML, 2 months). Short survival was predicted by transfusion requirement and other manifestations of severe cytopenia, as well as by myeloid immaturity. The presence or absence of sideroblastosis did not correlate with survival. Acute leukaemia developed in only eight patients (12%), six of whom initially had RA. Leukaemic transformation was not predicted by progressive cytological immaturity. This study demonstrates that even in the absence of leukaemic transformation, chronic myelodysplasia is a lethal haematological disorder.

Infection in the myelodysplastic syndromes

PURPOSE To determine the incidence, characteristics, and outcome of infection in patients with myelodysplastic syndromes (MDS) and risk factors that may lead to infection. PATIENTS AND METHODS We reviewed infections that occurred in 86 consecutive patients with MDS who received care from 1968 to 1986 at a university-affiliated Veterans Affairs Medical Center. Time lines charting the course of each patient with MDS were created and included infections, MDS subgroup at the time of presentation and at the time of each infection, peripheral neutrophil counts, and therapies for MDS. RESULTS Infections occurred at a rate of nearly one per patient year of observation. Infection rates were associated with MDS subgroup as follows: refractory anemia with or without ringed sideroblasts (RA +/- RS) less than refractory anemia with excess blasts (RAEB) less than RAEB in transformation (RAEB-T). The group of RA +/- RS patients who had erythroid abnormalities but minimal or no dyspoiesis of other cell lines had the lowest rate of infections. Infection rates were higher in patients with less than or equal to 1,000 neutrophils/microL blood than in patients with greater than 1,000 neutrophils/microL blood for each classifiable MDS subgroup. Neutrophil concentration and MDS subgroup were independent risk factors for infection in patients with MDS. Bacterial pneumonias and skin abscesses were the most common infections. Infection was the most common cause of death during MDS, accounting for 64% of deaths, and was more common than transformation to acute leukemia as a cause of death. CONCLUSION Infection is a common, life-threatening problem in patients with MDS. Neutropenia and MDS subgroup are each risk factors for infection. Clinicians should aggressively evaluate patients with fever and MDS for infection, especially pneumonia and skin infections.

Frequent Association of IgMλ with Crystalline Inclusions in Chronic Lymphatic Leukemic Lymphocytes

Abstract In four of 30 patients with chronic lymphocytic leukemia, studied by immunofluorescence, 1 to 31 per cent of peripheral blood lymphocytes were found to contain intracellular, rod-shaped inclusions that stained specifically for both μ and λ (IgMλ) determinants. Essentially all inclusion-containing lymphocytes exhibited monoclonal, membrane-bound IgMμ (M-IgM λ). However, only a minority of lymphocytes with M-IgM λcontained inclusions. On electron microscopy the homogeneous inclusions were found within the rough endoplasmic reticulum, and they exhibited an electrondense periodicity consistent with crystalline structure. In this series, the chance occurrence of crystals present solely in lymphocytes bearing M-IgMμ is 0.5 per cent. These studies indicate that in some patients with chronic lymphocytic leukemia, at least two morphologically distinct populations of neoplastic lymphocytes are present. (N Engl J Med 289:113–117, 1973)

Terminal transferase levels in chronic myelogenous leukemia in blast crisis and in remission

Abstract Terminal deoxynucleotidyl transferase (TdT) has been cited as a possible biological marker for acute lymphoblastic leukemia (ALL) and the blast phase of chronic myeloid leukemia (CML). In the present study high levels of TdT, comparable to levels present in normal thymus, were observed in circulating leukocytes of a CML patient in blast crisis. Sequential studies revealed disappearance of TdT from circulating leukocytes after remission was induced with vincristine and prednisone therapy. Blood TdT returned to moderately elevated levels in the absence of detectable circulating blasts, 5 months before the reappearance of blast crisis. During blast crisis the malignant cells were devoid of myeloid features on light and electron microscopy and were peroxidase negative and periodic acid-Schiff (PAS) positive. These studies demonstrate that elevated TdT levels may occur with or without detectable morphologic evidence of circulating blast cells. The presence of complement receptors on agranular blasts during the blast phase of chronic myeloid leukemia is a new finding.

Non-Hodgkin’s Lymphoma after Treatment for Hodgkin’s Disease

A patient is described who developed a diffuse histiocytic lymphoma (DHL) 9 years after radiation therapy for Hodgkins disease. This occurrence is of particular interest because the treatment for Hodgkins disease included no chemotherapy and the second tumor appeared to originate remote from the irradiated site. Thus, the role of Hodgkins disease treatment in the etiology of this patients second lymphoma appears doubtful. The development of DHL in this patient could represent an unrelated event or conceivably an event facilitated by Hodgkins disease itself.