In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden.

This randomized-controlled trial studied the efficacy of palifermin in a chemotherapy-only, high-dose Melphalan (HDM) transplant setting, to reduce oral mucositis (OM) and its sequelae measured by patient-reported outcomes (PRO) and medical resource use. Palifermin, relative to placebo was given either pre-/post-HDM or pre-HDM in patients with multiple myeloma (MM) undergoing auto-SCT at 39 European centers. Oral cavity assessment (WHO) and PRO questionnaires (oral mucositis daily questionnaire (OMDQ) and EQ 5D) were used in 281 patients (mean age 56, ± s.d.=8 years). 57 patients received placebo. One hundred and fifteen subjects were randomized to pre-/post-HDM receiving palifermin on 3 consecutive days before HDM and after auto-SCT and 109 patients were randomized to pre-HDM, receiving palifermin (60 µg/kg/day) i.v. for 3 consecutive days before HDM. There was no statistically significant difference in maximum OM severity. Severe OM occurred in 37% (placebo), 38% (pre-/post-HDM) and 24% (pre-HDM) of patients. No significant difference was observed with respect to PRO assessments or medical resource use, but more infections and fever during neutropenia were reported in pre-/post-HDM vs placebo (for example, 51 and 26%). To conclude, palifermin was unable to reduce OM or OM-related patient's burden in MM transplant patients.

The existence of lymphoid lineage restricted Philadelphia chromosome-positive acute lymphoblastic leukemia with heterogeneous bcr-abl rearrangement.

Analysis of lineage involvement was performed in 17 Philadelphia chromosome-positive acute lymphoblastic leukemia patients with no history of chronic myeloproliferative disorder. The percentage of blastic cells as defined by flow cytometry matched that of the Ph-positive cells in 14 out of 17 patients. The bcr-abl rearrangement was investigated by fluorescent in situ hybridization in morphologically identified blastic cells, myeloid elements, lymphocytes and erythroblasts using a combined light and fluorescent microscopical imaging. Lymphoid lineage restriction could be determined in all but three of the patients. These 14 patients exhibited heterogeneity in terms of m-bcr and M-bcr types of translocation as revealed by reverse transcription polymerase chain reaction. The three patients with multilineage involvement and M-bcr type of translocation reverted to chronic phase and the percentage of Ph-positive cells remained high. Thus, we could identify an uncommitted stem cell origin among Ph-positive ALLs only in those patients whose disease subsequently proved to be a lymphoid blastic crisis with clinically silent chronic phase.

[Treatment of chronic myeloid leukemia with interferon-alpha]. / Chronicus myeloid leukaemia kezelése interferon-alpha-val.

The authors have treated 38 patients with chronic phase chronic myeloid leukemia in their single center in the last five years. Conventional chemotherapy provided about 40-50% hematological response, interferon-alpha seems to be more effective, complete hematological remission occurred in 65%. Interphase cytogenetics and fluorescein in situ hybridisation technique was used to measure the cytogenetic response. They observed complete cytogenetic remission in two cases (8%), major response in 11 (39%), minor response in 4 (15%) and minimal response in 4 cases (15%). Interferon-alpha is an effective, well-tolerated medicine in the treatment of chronic myeloid leukemia.

[Hepatitis C virus infection and B-cell non-Hodgkin's lymphoma]. / A hepatitis C vírus-infekció és B-sejtes non-Hodgkin-lymphoma.

Oncogenesis is a multifactorial process in which environmental, genetical and infectious factors may be of importance. Specific viruses are supposed to have etiological role in about 15% of human tumors. Recently the B-cell proliferation inducing effect of the hepatotropic and lymphotropic hepatitis-C virus (HCV) came into the limelight based on the high prevalence of HCV positivity in B-cell non-Hodgkin's lymphoma (NHL) patients. The aim of the authors was to establish the prevalence of HCV infection in NHL patients. Paralelly the HBV, CMV and EBV markers, and the alterations of the humoral immune response (immunoglobulins, cryoglobulins, rheumatoid factor) were determined. 42 patients (24 male, 18 female; the mean age: 54.1 years, range 22-80 years) classified as 16 indolent (low risk), and 25 aggressive (intermediate risk) NHL and one with very aggressive Burkitt's lymphoma, according to the modified REAL classification were examined. Enzyme-linked immunosorbent assay (ELISA) for HBsAg and anti-HCV, HBsAg, anti EBV, anti CMV, furthermore polymerase chain reaction (PCR) for HCV-RNA were used. Anti-HCV was found in 6/42 NHL patients (14.3%), while anti-HCV and/or HCV-RNA PCR positivity revealed on overall HCV infection in 10/42 (23.8%) patients. None of them were HBsAg positive. Our findings support the hypothesis, that HCV might have an aetiological role in the lymphoproliferation leading to B-cell NHL.

[Analysis of T-cell receptor gamma-gene rearrangement in lymphoproliferative disorders using polymerase chain reaction]. / A T-sejt receptor gamma-génátrendezödés vizsgálata lymphoproliferativ kórképekben polimeráz láncreakció segítségével.

T-cell non-Hodgkin's lymphomas (NHL) exhibit a clonal T-cell receptor (TCR) gamma gene rearrangement as a result of sequential assembly of their variable (V gamma) and joining (J gamma) region segments. The analysis of the TCR gamma gene rearrangements may help to differentiate reactive lymphoproliferations from T-cell NHLs. The aim of this study was to reveal the usefulness of polymerase chain reaction (PCR) analysis of the TCR gamma gene rearrangement in the diagnosis of T-cell NHLs using native and formol-paraffin embedded tissues. The PCR amplification of the TCR gamma gene was performed by the V gamma specific sense and J gamma specific antisense primer pairs. The PCR products were evaluated by polyacrilamide gel electrophoresis containing ethidium bromide. The PCR analysis of the TCR gamma gene rearrangements has been performed in 95 lymphoproliferative disorders. The PCR analysis of the TCR gamma gene showed clonal gene rearrangement in 22 cases out of the 39 T-cell NHLs and in one case out of the 12 O-cell anaplastic large cell lymphoma but no clonal rearrangements were detected in any of the 15 reactive lymphoproliferations or 13 B-cell NHLs. Thus, clonal TCR gamma gene rearrangements was detected by PCR in 58.2% of T-cell NHLs but no clonal TCR gamma gene rearrangements were shown in any of reactive lymphoproliferations of B-cell NHLs. These studied showed that the PCR amplification of the TCR gamma gene can be a powerful tool in the diagnosis of T-cell NHLs.

Myeloid leukemia and myelodysplastic syndrome relapsing as granulocytic sarcoma (chloroma) after allogeneic bone marrow transplantation.

Of 229 consecutive patients receiving allogeneic blood or bone marrow stem cell transplants for acute myeloid leukemia, chronic myeloid leukemia, or myelodysplastic syndrome between 1974 and 1996, 52 patients relapsed. The original tumor recurred as granulocytic sarcoma (chloroma) in three patients (1.3%). Chloroma was found in the ovary in two patients and in the central nervous system in one patient. None of these three patients had experienced > or = grade II acute or more than limited chronic graft-versus-host disease. The intervals between transplantation and recurrence with chloroma were 2, 6, and 13 years. Two patients received a second transplant, and all three died of treatment sequelae.

Changes in adhesion molecule expression and function in B-cell chronic lymphocytic leukaemia after in vitro interferon-alpha stimulation.

Peripheral blood mononuclear cells (PBMCs) from 10 B-CLL patients were investigated after 24 hours of in vitro interferon-alpha (IFN-alpha) stimulation. The constitutional expression of the L-selectins (LECAM-1), LFA-1/CD11a, VLA alpha-4/CDw49d and ICAM-1/CD54 adhesion molecules was detected, and changes in their density after IFN-alpha stimulation were compared to results obtained by the high endothelial venule (HEV)-binding assay and a carbohydrate (phosphonomannan core polysaccharide: PPME and fucoidin) immobilization test. The LECAM-1 and ICAM-1 molecules were expressed on the great majority of CLL cells, while the LFA-1 and VLA-4 alpha-chains were expressed by only a small number of cells. Statistically significant changes (p < 0.001) were observed in LECAM-1 antigen density (changes in mean cell fluorescence), as well as in functional tests (HEV-, PPME- and fucoidin-binding; p < 0.01) after in vitro IFN-alpha stimulation. Based on a prior study (Jewell et al., Leukemia 1992: 6: 400-404) and on the present findings, not only an increased expression but also an enhanced function of the L-selectins seem to be well substantiated after IFN-alpha stimulation, which may explain the therapeutic effect of IFN-alpha in reducing the accumulation of leukaemic B cells in the blood. The remarkably high expression of ICAM-1 in this series necessitates further studies to clarify the exact expression rate and role of this molecule.

Expression and function of L-selectin molecules (LECAM-1) in B-cell chronic lymphocytic leukemia.

BACKGROUND: The notion that adhesion molecules play a crucial role in lymphoma/leukemia dissemination is widely accepted. Individual cases of B-cell chronic lymphocytic leukemia (B-CLL) show well-defined variables in the extent and pattern of peripheral blood and nodal involvement. The L-selectin adhesion molecule (TQ1/Leu-8, LAM series and LECAM-1) initiates the attachment of lymphocytes to the high endothelial venules (HEVs), and as a consequence the entrance of lymphocytes from the blood into the peripheral lymph node (recirculation which may be operative in lymphoma/leukemia dissemination as well). MATERIALS AND METHODS: The constitutional expression of L-selectin molecules (LECAM-1) on peripheral blood mononuclear cells (PBMCs) from B-CLL (16 cases) was examined and correlated with receptor function in an HEV-binding assay and in a ligand immobilization test. RESULTS AND CONCLUSIONS: A correlation was found between constitutional expression and function of the L-selectins, namely the higher the number of cells expressing L-selectin molecules at a measurable level on the cell surface, the greater the number of cells showing attachment in the tests. It is suggested that many aspects of the biological and clinical heterogeneity of B-CLL will be explained by revealing the exact adhesion profile and function in different subtypes of the disease.