Warm red blood cell autoantibodies and clinical diagnoses in patients with or without autoimmune hemolysis.

OBJECTIVES: Red blood cell autoantibodies (RBC autoAbs) of IgG class are found in the majority of patients with warm autoimmune hemolytic anemia (wAIHA) but sometimes also during the pretransfusion testing of patients with different diagnoses but without hemolysis. The aim of the study was to identify the main differences between these two groups of patients according to age, gender, subclass and titer of IgG RBC autoAbs and diagnosis. MATERIAL AND METHODS: In the 9-year retrospective study, data were collected from records of 291 patients with IgG RBC autoAbs detected by gel technique, from which 111 with wAIHA. RESULTS: More than 85% of patients in both groups were over 40 years old, with male to female ratio 1:1.9 in wAIHA vs 1:1.3 in patients without hemolysis (P=0.0916). The main characteristics of patients with wAIHA vs patients without hemolysis were: IgG only 38% vs 70%, IgG+Complement 62% vs 30%, total IgG1 79% vs 55%, IgG1+IgG3 35% vs 11%, titer of 100 for IgG1+IgG3 17% vs 3% (P<0.0001), respectively, while titer of 100 for IgG1 18% vs 9% (P=0.0241). The underlying diagnosis in wAIHA vs patients without hemolysis: hematologic disorders 41% vs 22% (P=0.0006), autoimmune disorders 12% vs 13% (P=0.8033), solid tumors 5% vs 14% (P=0.0154) and surgery procedures 6% vs 26% (P<0.0001). CONCLUSION: We observed more wAIHA patients with high titer of IgG1 and high prevalence of IgG1+IgG3 and consider that patients without hemolysis having identical results might be interesting to find out how they are protected from damage by RBC autoAbs.

Pneumomediastinum as a complication to treatment of mediastinal (thymic) large B-cell lymphoma.

Mediastinal (thymic) large B-cell lymphoma (Med-DLBCL) is a subtype of diffuse large B-cell lymphomas (DLBCL) with a typical radiological appearance of bulky anterior mediastinal mass, often with areas of necrosis. We report a case of Med-DLBCL with unusual radiological findings and clinical development. Computed tomography (CT) obtained at presentation revealed a huge anterior mediastinal tumor with an axial diameter of 180 mm. Nineteen days after the first cycle of chemotherapy, chest radiography and CT revealed large areas of tumor necrosis and pneumomediastinum with air-fluid levels. To our knowledge, air-fluid levels inside Med-DLBCL have not been previously described. This finding, in combination with necrotic sputum, may indicate communication between the tracheobronchial tree and the tumor.

Clinical tumor cell distribution pattern is a prognostically relevant parameter in patients with B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) cells are variably distributed among the major lymphoid compartments contributing to the heterogeneous clinical presentation and course of this disease. In order to evaluate this variable distribution we propose a model for its clinical assessment. DESIGN AND METHODS: We introduce the model for tumor distribution (TD) assessment based on TTM scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM). TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%, predominantly leukemia if TD=50-99% and predominantly lymphoma TD<50%. RESULTS: Among 341 B-CLL patients there were 22.6%, 55.1%, 22.3%, pure leukemia, predominantly leukemia and predominantly lymphoma cases, respectively. TD parameter was strongly associated in univariate analysis with TTM size, Rai and Binet stages, spleen size and beta(2) microglobulin. TD was associated with response to therapy and survival, with higher TD values translated into higher response rates and longer survival. However, in univariate and multivariate Cox analysis TD displayed much stronger relationship with prognosis in female patients, where it is the strongest independent predictor of survival along with age and Binet stage. INTERPRETATION AND CONCLUSIONS: TD, a quantitative and simple clinical parameter, easily assessed in all patients, offers a reliable tool for evaluation of tumor cell distribution in B-CLL. It has independent and strong prognostic power in females, as opposed to males, possibly unmasking important, yet unrecognized, biological difference in B-CLL patients.

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna.

BACKGROUND: In recent years, much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced, progressive B-cell chronic lymphocytic leukemia (CLL) patients. For this reason, the International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia Cooperative Group, has begun a randomized multicenter trial comparing Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with continuous high dose chlorambucil (HD-CLB). METHODS: During the period January 1987 to May 1993, 228 previously untreated CLL patients from 7 cooperative institutions were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (> 9), and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The response to therapy was defined by reduction of the initial TTM score. The end points of the trial were response rate, survival, and toxicity. RESULTS: HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response+partial response) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 68 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms. CONCLUSIONS: The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients with advanced and/or progressive CLL. Therefore, the authors recommend its wider use, possibly in comparison with and/ or in combination with new therapeutic agents, such as purine analogues.

2-Chlorodeoxyadenosine treatment in non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia resistant to conventional chemotherapy: results of a multicentric experience. International Society for Chemo-Immunotherapy.

Among the purine analogs, 2-chlorodeoxyadenosine (2-CDA) is particularly effective for the treatment of hairy cell leukemia and Waldemstrom's macroglobulinemia. Both efficacy and toxicity of 2-CDA were evaluated in previously treated patients affected with chronic lymphoproliferative disorders such as low-grade non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). Thirty cases, mainly refractory, 16 affected with CLL, were included from six centers of the International Society for Chemo-Immunotherapy (IGCI). 2-CDA was administered in a 2 h i.v. infusion for 5-7 days at the standard dose of 0.1 mg/kg/day every 4 weeks. The median number of cycles was 3. Of 30 cases, eight (26.7%) achieved a complete remission (CR), nine (30%) a partial remission (PR), and two (6.7%) a minor response, while five cases (16.6%) did not respond, and six (20%) were considered early deaths. The overall response rate (CR + PR) was 56.7%, with a median response duration of 12 months (range 3-28 +) and a better response in CLL patients. Considering that the majority of patients were heavily pretreated, toxicity was acceptable, with 40% of cases not presenting any toxic effect. The main toxicity consisted in infectious complications. Based on the results of the present study, we confirm that 2-CDA is an effective drug in these lymphoproliferative disorders, suggesting its possible use either alone or in combination, also as first-line therapy.

Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: long-term results of a randomized trial.

In 1982 the IGCI CLL cooperative group decided to investigate the usefulness of treating, at diagnosis B-cell chronic lymphocytic leukemia (CLL) in early and stable phase of the disease. From January 1982 to December 1986, 148 patients were randomized either to receive immediate treatment with chlorambucil (CLB) or to defer therapy to the time of progression. The early and stable phase of the disease was defined by a total tumor mass (TTM) score < 9, the absence of anemia or thrombocytopenia and a doubling time > 12 months. The main end-point of the study was survival. At the last evaluation in April 1993, after a median follow-up of 75 months, no significant difference was found in overall survival between early vs. deferred treatment patients from every cause of death as well as from death due to CLL-related causes only. The same results were obtained when the patients in more favorable stages, such as Binet stage A and TTM < 4.5, were considered. Interestingly, the incidence of epithelial cancer was similar in the two groups. Early treatment was associated with a significantly better response and a lower progression rate. From this long-term experience, it can be concluded that immediate chemotherapy with CLB is not beneficial for CLL patients in early and stable phase of the disease in terms of survival.

The differential diagnostic capacity of serum amyloid A protein between infectious and non-infectious febrile episodes of neutropenic patients with acute leukemia.

We studied the behavior of four major acute phase proteins (SAA, CRP, ACT and AGP) in pyrexial occurrences of 16 neutropenic patients with acute leukemia. Altogether 37 febrile episodes were recorded; 27 were infectious in origin (microbiologically documented infection and clinically documented infection, MDI/CDI group) and 10 were pyrexias of unknown origin (PUO group). In the MDI/CDI group the mean value for the highest individual SAA concentration was 282 +/- 161 mg/l and in the PUO group 95 +/- 79 mg/l. The corresponding mean values were 4.0 mg/l (range 0.2-5.5 mg/l) in 10 control patients with 1 year remission and 0.8 mg/l (range < 0.1-1.2 mg/l) in 30 healthy adults. The peak value of SAA rose above 100 mg/l in 85% of our MDI/CDI pyrexias and in 40% of PUO. More reliable results were obtained when the difference between the value on the day when pyrexia occurred and the previous day was calculated. In that case, the difference was above 75 mg/l in 23 of 27 (85%) MDI/CDI pyrexias and in none of 10 (0%) PUO. In the MDI/CDI group the mean difference was 204 +/- 137 mg/l while it was only 26 +/- 19 mg/l in the PUO group. The statistical significance was very high (p < 0.0001). The CRP monitoring was very inferior to SAA while ACT and AGP monitorings were unsatisfactory.

The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases.

The roles of age and sex and their relationship to other prognostic factors were studied in 117 chronic myeloid leukaemia (CML) and in 256 chronic lymphocytic leukaemia (CLL) patients. Survival in CML was not related either to age at diagnosis or to sex. In contrast, the CLL patients classified into four age strata (less than 50, 50-59, 60-69, greater than 70 years) had an expected median survival (EMS) of 142, 101, 85 and 33 months respectively (chi 2 for heterogeneity = 35.59, P less than 0.0005; chi 2 for trend = 25.09, P less than 0.0005). Prognostic power was independent of sex, Rai stages, total tumour mass score (TTM), TTM distribution pattern, anaemia, thrombocytopenia, serum immunoglobulins and response to therapy. The relative survival rate (the ratio of patient's EMS and EMS in age- and sex-matched general population) was 0.40 in CLL patients and 0.13 in CML patients. Relative survival was more reduced in older CLL patients than in younger ones (0.37 vs 0.47, respectively), whereas relative survival was less reduced in older CML patients than in younger ones (0.18 vs 0.12, respectively). The results show that the age is a significant independent prognostic factor in CLL but not in CML. The difference in the effects of age on prognosis in CLL and CML most probably reflects the fundamental differences in their respective pathogeneses.

[Relation between clinical parameters and histologic findings in patients with non-Hodgkin's lymphoma]. / Odnos klinickih parametara i histoloskog nalaza u bolesnika s ne-Hodgkinovim limfomom.

Clinical and morphological findings of lymph nodes in 150 consecutive untreated non-Hodgkin lymphoma (NHL) patients were retrospectively studied. One hundred and fifteen (77%) patients had B-NHL and 35 (23%) T-NHL, 96 (64%) patients had NHL low grade malignancy and 54 (36%) NHL of high grade malignancy according to the Kiel classification. Lymph nodes exceeding 2 cm in diameter (p less than 0.05), hepatomegaly (p less than 0.05), splenomegaly (p less than 0.05), and the duration of lymphadenopathy for more than 6 months preceding diagnosis (p less than 0.01) were significantly more common in low than high grade malignancy of NHL patients. Febrile episodes at the diagnosis were significantly more common in high than in low grade malignancy of NHL patients (p greater than 0.05). Lymph nodes exceeding 2 cm in diameter (p less than 0.05) in B-NHL, and lymph nodes above the diaphragm (p less than 0.05) and skin infiltration (p less than 0.001) were more common in T-NHL than in B-NHL patients. At the diagnosis low grade NHL patients have significantly more often splenomegaly, hepatomegaly, large palpable lymph nodes, and long lasting lymphadenopathy before diagnosis. High grade malignancy NHL patients have more often general symptoms, B-NHL patients have more often large palpable lymph nodes, T-NHL patients have more often skin infiltration and lymph nodes above the diaphragm. Precise clinical characterization of patients in addition to pathohistological diagnosis are very important in this highly variable disease.

High dose ARA-C as induction therapy of acute myeloid leukaemia.

Twenty-one newly diagnosed adult AML patients were treated with high dose Ara-C (HD-ARA-C) as a single induction treatment with the dose of 2 g/m2 q 12 hours x 12. Seventy-six percent (16/21) responded with complete remission. Three patients died in induction in pancytopenia, another one died on day 44 in CR due to bleeding of pulmonary aspergilloma. This treatment seems to be highly efficient for remission induction, but requires an adequate transfusion and other supportive measures. The overall toxicity was transient and seems acceptable. However, the remission duration is unacceptably short, the consolidation with the same treatment seems to be inadequate. More aggressive treatment in postinduction period seems to be warranted.