HLA-DR2 frequency increase in severe aplastic anemia patients is mainly attributed to the prevalence of DR15 subtype

The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.     

Sotatercept in patients with osteolytic lesions of multiple myeloma

This phase IIa study evaluated the safety and tolerability of sotatercept, and its effects on bone metabolism and haematopoiesis in newly diagnosed and relapsed multiple myeloma (MM) patients. Patients were randomized (4:1) to receive four 28‐d cycles of sotatercept (0·1, 0·3, or 0·5 mg/kg) or placebo. Patients also received six cycles of combination oral melphalan, prednisolone, and thalidomide (MPT). Thirty patients were enrolled; six received placebo and 24 received sotatercept. Overall, 25% of patients received all four sotatercept doses; 71% of sotatercept‐treated patients had ≥1 dose interruption mainly due to increases in haemoglobin levels. Grade ≥3 adverse events (AEs) were reported in 17% of patients receiving placebo and 58% receiving sotatercept. Grade 4 AEs in sotatercept‐treated patients were neutropenia, granulocytopenia, and atrial fibrillation (one patient each). In patients without bisphosphonate use, anabolic improvements in bone mineral density and in bone formation relative to placebo occurred, whereas bone resorption was minimally affected. Increases in haemoglobin levels, versus baseline, and the duration of the increases, were higher in the sotatercept‐treated patients, with a trend suggesting a dose‐related effect. Multiple doses of sotatercept plus MPT appear to be safe and generally well‐tolerated in MM patients.     

Retrospective analysis of the morphological, cytochemical, cytogenetic, electron microscopic, and biochemical features of blast cells in acute promyelocytic leukemia

The paper presents a retrospective analysis of long-term follow-ups (from 1959 to 2000) of 86 patients with acute pro-myelocytic leukemia, a rare type of hemoblastoses. The specific features of this form of leukemia is that blast cells of the bone marrow and peripheral blood have a specific granularity that plays a decisive role in the development of the severe hemorrhagic syndrome leading to patients' death. The morphological, cytochemical, cytogenetic, electron microscopic, and biochemical features of blast cells in this disease and its pathogenesis, clinical presentation, and treatment are considered. An extract from the records of a female patient who has had a complete clinical and hematological remission for 22 years is given. The follow-up of such a prolonged remission has not been covered in the Russian literature.     

Incidence and characteristics of complications in aplastic anemia patients treated with antilymphocytic globulin

AIM: To examine frequency and characteristic features of complications arising in administration of domestic antilymphocytic globulin (ALG) in patients with aplastic anemia (AA). MATERIAL AND METHODS: From 1980 to 2000 125 patients with AA were treated with ALG made in Russia. Two and three courses of ALG were performed in 25 and 8 patients, respectively. RESULTS: The treatment was complicated most often with allergic reactions (AR) observed in 42.4% patients, hemorrhagic syndrome (HS) and infectious complications (IC). Goat ALG was more allergic than rabbit ALG (46.2 vs 34.6%, respectively). If the second course was made with ALG of the same kind, AR occurred in 37.5% patients while ALG of the different kind produced complications only in 11.8% patients. HS was recorded in 37.3% patients, its frequency was unrelated to ALG kind and was not severe (71.2%). IC occurred in 16.5% patients, their occurrence was also unrelated to the ALG kind and were of the first degree in 63.6%. CONCLUSION: Domestic ALG often results in AR. To reduce frequency and severity of complications in ALG treatment, it is recommended to use long intravenous infusions (12-18 h) and change ALG kind in subsequent ALG courses.     

Low doses of alpha-interferon preparations in the treatment of patients with chronic myeloleukemia

AIM: To compare the effects of low-dose alpha-interferons with those of cytostatics (hydroxyurea or myelosan) on survival of patients and duration of chronic phase of chronic myeloid leukemia (CML). MATERIAL AND METHODS: 107 CML patients were divided into two groups. 28 patients (15 males and 13 females) aged 17-59 entered group treated with alpha-interferon drugs. 79 control patients (35 males and 44 females) aged 15-79 received standard chemotherapy (hydroxyurea or myelosan). RESULTS: 3-year survival in the study group and controls was 94 and 67.5%, respectively. 5-year survival--70.8 and 28.9%, respectively. The survival medians for the groups were 66 and 48 months, respectively. 36 months after CML diagnosis, chronic phase of the disease still continued in 90.2% of the study group patients and in 53.4% of patients on chemotherapy. 54 months after the diagnosis the chronic phase was registered in 56.5 and 24% of patients, respectively. The medians made up 54 and 39 months, respectively. CONCLUSION: Treatment of CML with low-dose alpha-interferons increases duration of the CML chronic phase and survival of CML patients.     

Diagnostic and prognostic significance of blood-serum ceruloplasmin, acetylcholinesterase and total proteolytic activity in patients with multiple myeloma]

The study included 82 patients with multiple myeloma (MM) to evaluate the diagnostic and prognostic significance of correlation between of levels of ceruloplasmin (CP), acetylcholinesterase (ACE) and total proteolytic activity (TPA) in blood serum and immunochemical pattern, tumor mass and response to chemotherapy. It was shown that CP, ACE and TPA determination may be used as additional markers to confirm therapeutic benefits, to timely detect relapse and to verify resistance to chemotherapy. It was also demonstrated that resultant decrease in CP and TPA and increase in ACE levels are reliable indicators of changes developing in MM course and remission fulfillment. High values for CP and low ones for ACE point to pathological activity. Both diagnostic and prognostic significance of the indices has been shown. The highest levels of CP and TPA in blood serum were identified in cases of A-myeloma and myeloma of Bence Jones while ACE concentrations in those patients were lower than in G-myeloma which correlated with median survival. Application of said assays might improve diagnosis, management and prognosis of MM.     

Treatment of chronic lymphocytic leukemia in relation to clinico- morphological characteristics of the disease

Marrow histomorphometry was performed in 73 untreated chronic lymphoid leukemia (CLL) sufferers. Follow-up results are available for 36 of them: 25 treated and 11 untreated with chemotherapy. The method of marrow histomorphometry allows recognition of three CLL forms: diffuse, diffuse-focal and focal; helps to determine indications to chemotherapy, assess its efficacy, prognosticate the disease course; is more reliable than clinical and laboratory findings.