Mirando Mrsić

Acute promyelocytic leukemia M3: cytomorphologic, immunophenotypic, cytogenetic, and molecular variants.

Acute promyelocytic leukemia (APL) M3 is an acute myeloid leukemia (AML) subtype characterized by proliferation of malignant promyelocytes with mature myeloid immunophenotype and the translocation t(15;17)(q22;q11), which results in the fusion of retinoic acid receptor-alpha (RARalpha) gene on chromosome 17 and the gene PML on chromosome 15. There are three M3 morphologic variants: the typical hypergranular form and the microgranular and basophilic variants. Although most leukemic cells in M3 patients express t(15;17), other cytogenetic abnormalities have also been reported. Also, there are three molecular variants of the PML/RARalpha transcript (bcr1, bcr2, bcr3). Blasts had typical hypergranular appearance (13 patients) with a mature myeloid immunophenotype (HLA-DR(-),CD13(+), and/or CD33(+)) (10 patients) in the majority of patients with M3 followed in this study. The typical translocation [t(15;17)(q22;q11)] was detected by cytogenetic analysis in 5 M3 patients, but PML/RARalpha was positive in 13 out of 15 patients, as assessed by RT-PCR (8 patients with bcr1 and 5 with bcr3 subtype). Cytogenetic diversity was found in three patients (1 with t(17;17), 1 with +8, and 1 with add (7)(q22); -7; +8). According to many studies, leukemic cell heterogeneity in APL influences the clinical outcome of disease. The analysis of certain leukemic cell characteristics on the clinical outcome in our study revealed that patients with bcr3 had shorter medians of first remission and survival in comparison to patients with the bcr1 isoform of PML/RARalpha. Also, the clinical relapse of disease in 4 APL patients with reverted PML/RAR alpha positivity is consistent with the view that detection of PML/RARalpha by RT-RCR in patients in remission implies a poor prognosis. On the contrary, lack of detection of PML/RARalpha by RT-PCR at least three times is a sign of long remission and survival.

Haematological malignancies in childhood in Croatia: Investigating the theories of depleted uranium, chemical plant damage and 'population mixing'

Some of potential causes proposed to explain the reported increase of haematological malignancies in childhood during or after the war period in several countries include depleted uranium, chemical pollution and population mixing theory. The aim of this study was to define the population of Croatian children aged 0–14 years who were potentially exposed to each of those risks during the war and to investigate any possible association between the exposure and the incidence of haematological malignancies. The authors analyzed the data reported by the Cancer Registry of Croatia during the pre-war period (1986–1990), war period (1991–1995) and post-war period (1996–1999). In the group of 10 counties potentially exposed to depleted uranium and two counties where chemical war damage occurred, no significant difference in incidence of the studied haematological malignancies was noted in comparison to pre-war period. The incidence of lymphatic leukaemia significantly increased in four counties where population mixing had occurred during the war period, supporting the ‘mixing theory’. In those counties, the incidence of Hodgkins lymphoma decreased during and after the war. In Croatia as a whole, decreases in incidence of myeloid leukaemias during war and non-Hodgkin lymphoma after the war were noted.

Gemcitabine in the treatment of relapsed and refractory Hodgkin´s disease

Background: Patients with refractory Hodgkin’s disease or relapsing after high-dose therapy and autografting have a poor prognosis. Here, we present our experiences with gemcitabine in this setting. Patients and Methods: We treated 14 patients with relapsed or refractory Hodgkin’s disease with gemcitabine. The treatment was given on a compassionate use basis, off-label and not according to a study protocol. Patients were 17-46 years of age. 1 patient had stage IA disease, 2 patients had stage IIIB disease and 11 patients had stage IVB disease. 9 patients had received radiotherapy. 8 patients had been autografted and 1 patient auto- and allografted. Gemcitabine was administered at a starting dose of 1 g/m2 on days 1 and 8 every 3 weeks in combination with steroids. Results: The median follow-up period was 10 months. Hematological toxicity grade 3-4 occurred in 12 patients leading to dose reductions. 1 patient died of neutropenic sepsis. No other non-hematological toxicities were observed. The response rate was 64% with 6 patients achieving complete remission (CR) and 3 patients partial remission (PR). The median time to treatment failure was 9 months, and survival was 11 months. Responses were seen in previously transplanted patients and in patients refractory to previous treatment. The so far longest responder has been in CR for over 68 months. Conclusion: Gemcitabine is an effective treatment for Hodgkin’s disease. Heavily pretreated patients often require dose reductions.

Morganella morganii causing fatal sepsis in a platelet recipient and also isolated from a donor's stool

Summary.  Bacterial contamination of blood products causes significant patient morbidity and mortality. Contaminated platelet transfusion is a frequent cause of bacteraemia and sepsis because of the storage conditions of platelets. A fatal case of Morganella morganii platelet transfusion associated with sepsis is described, along with procedures traced back to the isolation of M. morganii from a donors stool. Molecular typing was performed, and the same M. morganii strain was found in blood and post‐mortem organ cultures of platelet recipient and platelet bag and in the donors stool. The route of contamination is unknown. The contamination could be due to either insufficient venipuncture site disinfection or the donors transient bacteraemia. Patient died 5 days after the transfusion.

Relation between urinary cytology abnormalities and Cyclosporine A therapy in bone marrow transplant recipients

The aim of the study was to determine the relationship, if any, between abnormalities in urinary cytology and the administration of cyclosporine A in bone marrow transplant recipients. Specific attention was given to the presence of tubular cells with round inclusions (TCRI). Two bone marrow transplant recipient groups were studied: one with allogeneic bone marrow transplantation (BMT) (20 patients) who were treated with cyclosporine A, and the other with autologous BMT (12 patients) who did not receive cyclosporine A. Urinary cytology showed TCRI in 41.66% of the patients after autologous BMT and in 80% of the patients after allogeneic BMT. In the group of patients treated with allogeneic BMT, the occurrence of TCRI was associated with a high incidence of glycosuria and was followed by an increase in the blood level of cyclosporine A, an increase in the serum creatinine concentration and a decrease in the creatinine clearance. These results demonstrated that TCRI, although related to, were not found to be exclusively specific to the administration of cyclosporine A.

Splenectomy? No, thank you!

Because of an extremely enlarged spleen, splenectomy was considered in a 60-year-old man with a 3-year history of osteomyelofibrosis and slightly depressed blood cell counts. Scintigraphic study with 99mTc-antigranulocyte antibodies (AGAb) was performed with a view to estimating the spread and activity of haematopoietically active bone marrow. Figure part a shows whole-body scans of the patient, without visible haematopoietic activity in the bones, and with prominent extramedullary haematopoiesis in the enlarged spleen. Figure part b shows normal bone marrow distribution in another patient. The accumulation of the AGAb in the spleen and liver is low and very variable: in normal patients 4 h after injection it amounts to about 6% of the injected activity in the spleen and up to 10% in the liver [1]. After the findings documented in a, splenectomy was cancelled. This case demonstrates all the benefits of AGAb. This method allows us to analyse the distribution and function of haematopoietically active bone marrow [2], the spread and activity of infection or inflammation [3] and, in addition, the status of the spleen [4]. References