Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection.

BACKGROUND: Prolonged chemotherapy-induced neutropenia is a major risk factor for the development of severe bacterial and fungal infections. Infectious manifestations may progress despite adequate anti-infectious treatment and lead to a very high short-term mortality. Granulocyte transfusion (GT) therapy is often considered. However, its efficacy is not well documented. METHODS: We retrospectively analyzed the clinical characteristics and outcome of a cohort of patients with haematological malignancies receiving GT during neutropenia and severe infection. RESULTS: A total of 30 patients with a median age of 46 y (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%) and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All patients had severe and prolonged (median 16 days) neutropenia. The major indications for GT were persistent fever and clinical deterioration despite broad anti-infectious therapy, in combination with progressive pneumonia (n = 16), neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were given for a median of 3 transfusions (range 1-14). The median time to fever defervescence after GT was 14 days (range 6-33 days). For 11 patients, the resolution of fever and all signs of infection could directly be related to GT, and 3 of these patients became long-term survivors. Mortality at 30 days post-GT was 40% and at 6 months post-GT was 72%. GT was well tolerated. CONCLUSIONS: A substantial proportion of severely ill neutropenic patients appeared to benefit from GT. The results further underline the need for well- designed, randomized, prospective trials to determine the efficacy of this intervention in patients with life-threatening infectious complications.

T-cell-rich B-cell lymphoma - diagnostic and therapeutic aspects.

BACKGROUND: Morphologically, T-cell-rich B-cell lymphoma (TCRB-NHL) may be indistinguishable from Hodgkin's disease (HD). Immunophenotyping may be helpful in the separation of these entities. TCRB-NHL is occasionally misdiagnosed and treated as HD. However, information is limited regarding clinical characteristics and outcome of this patient population. Furthermore, knowledge concerning any association with Epstein-Barr virus (EBV) in TCRB-NHL, as well as the immunophenotype of reactive T-cells and the expression of T-cell intracellular antigen-1 (TIA-1), granzyme B (GrB) and the CD3-zeta-chain is limited. PATIENTS AND METHODS: We have re-evaluated 251 tumour biopsies from patients aged > or =15 years with HD diagnosed 1985-1994. Reclassification from HD to TCRB-NHL was done in 12 cases (5%). Six TCRB-NHL patients initially diagnosed and treated as B-NHL were also included. All TCRB-NHL biopsies were analysed for latent membrane protein 1 (LMP-1), CD4, CD8, CD56, CD57, TIA-1, GrB and CD3-zeta-chain. RESULTS: Twelve cases of TCRB-NHL were initially subclassified as HD (lymphocyte predominance 5, nodular sclerosis 3, and mixed cellularity 4). Of these 12 TCRB-NHL patients, 6 were given radiotherapy alone, 5 MOPP/ABVD or similar combination chemotherapy, and one patient combined modality treatment. Male sex (p<0.05) and inguinal involvement (p<0.001) were significantly more frequent when TCRB-NHL patients receiving HD treatment (n=12) were compared with the remaining patients with confirmed (conf) HD, while no significant differences were seen with regard to stage, bone marrow infiltration, splenomegaly or cause-specific survival. Similar results were achieved when all TCRB-NHL patients (n=18) were compared to conf HD patients. Lymphoma cells in three samples stained positively for LMP-1. A decreased expression of CD3-zeta-chain was seen in 9/14 tumour biopsies. CONCLUSION: Immunohistochemistry makes it possible to identify cases of TCRB-NHL that are morphologically difficult to distinguish from HD. The outcome of TCRB-NHL patients treated as having HD was comparable with that of the remaining HD population.

A prospective comparison of fine-needle aspiration cytology and histopathology in the diagnosis and classification of lymphomas.

INTRODUCTION: Surgical biopsy examination is the gold standard for lymphoma diagnostics. However, fine-needle aspiration cytology (FNAC) offers several advantages in that it is quick, inexpensive, and the aspiration procedure has very few complications. This prospective study compares the diagnostic outcome between FNAC and surgical biopsy. MATERIALS AND METHODS: A total of 103 patients (>15 years) with lymphadenopathy and accessible lymph nodes underwent both diagnostic procedures. Immunophenotyping was performed on both FNAC and histopathological specimens. The updated KIEL classification was used for primary diagnosis and the WHO classification for reclassification. RESULTS: FNAC- and histopathology-based diagnoses were concordant in 76 patients. In 10 patients, there was a major diagnostic discordance: four differed with regard to degree of malignancy (low- versus high-grade NHL), three lymphoma versus reactive changes, and three regarding Hodgkin's lymphoma versus anaplastic large cell lymphoma. In 10 patients there was some (minor) discordance regarding subclassification: in eight patients the results of immunophenotyping differed, in two cases there were discrepancies in the cell type classification. In the remaining seven cases, there were diagnostic difficulties due to an insufficient sample. two serious adverse events occurred following surgical biopsy. CONCLUSIONS: FNAC is an accurate method in the diagnosis of lymphomas when the cytologic diagnosis is corroborated by immunophenotyping. However, an increasing use of FNAC for primary diagnosis and classification of lymphomas may result in a loss of archival tissue for complementary analyses, reclassification, and research purposes. In addition, some of the lymphoma entities are impossible to diagnose with use of the FNAC technique.

Recognition of intercenter differences may help develop best practice.

The Swedish Apheresis Registry is a National Quality Registry and performing intercenter comparisons can be done as one task. The purpose of this study was to evaluate differences in adverse effects (AE) associated with plasma exchange (PE) for the development of best practice. Six hundred and twenty reports of AE related to a total of 12,461 apheresis procedures performed during 1996-2002 were analyzed, and eight Swedish university hospital centers that reported AE every year were compared. About 70% of all PE in Sweden were performed in centers that also reported AE. During this period, there was no change in the proportion of PE procedures with AE, but there was a decrease in the frequency of prematurely interrupted procedures (2.1% to 1.3%, P = 0.003). The mean frequency of moderate and severe AE was 5%. Adverse effects were more common when PE was performed in patients with Guillain-Barré syndrome (GBS; 10%) or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS; 8%) than in patients with macroglobulinemia/hyperviscosity syndromes (2%). In the eight centers, there was a four-fold difference in AE between the centers with the highest and the lowest frequency. The frequency of AE in GBS, TTP-HUS and macroglobulinemia/hyperviscosity syndromes differed four-fold, while the frequency of specified symptoms differed more than four-fold. The indications and the choice of substitution fluids could explain some of these differences. The results of the study have initiated changes in practice. The identification of significant intercenter differences in the frequency and symptoms of AE has started improvement in current PE practices.

Characterization of red cell autoantibodies in consecutive DAT-positive patients with relation to in vivo haemolysis.

The clinical symptoms of patients with autoimmune haemolytic anaemia (AIHA) may range from no symptoms at all to severe haemolysis with life-threatening anaemia. The aim of the present study was to characterize the autoantibodies serologically and to evaluate their activity in vitro in monocyte monolayer assay (MMA) in consecutive direct antiglobulin test (DAT)-positive patients from a haematological department. We also aimed to evaluate the monocyte production of cytokines in vitro and relate all findings to in vivo haemolysis. Twenty-nine patients with positive DAT were included in the study and clinical characteristics were documented. The patients were divided into three groups based on laboratory parameters, severe haemolysis, moderate haemolysis and no sign of haemolysis. Severe haemolysis was related to a strongly positive DAT and positive results in MMA. When eluates were analysed in MMA, a positive result was associated with a higher concentration in the supernatants of interleukin (IL)-8 after 6 h incubation. We conclude that MMA activity and in vitro cytokine production may reflect the in vivo activity of autoantibodies. This may be of importance in understanding the mechanisms of haemolysis and in predicting the harmfulness of antibodies, especially when blood transfusions are needed.

Hodgkin's lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis.

BACKGROUND AND OBJECTIVES: In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than do younger ones. Inadequate therapy, often due to decreased tolerance to treatment, contributes to the poor outcome. This study was undertaken to evaluate potential clinical factors of importance for prognosis with special reference to relative dose intensity (RDI) of chemotherapy (CT). DESIGN AND METHODS: Eighty-eight consecutive elderly (>60 years) HL patients diagnosed between 1973-1994 who received up-front CT+/-radiotherapy (RT) were included (median age 72 years, range 60-92; median follow-up time 78 months, range 49-206). The calculations of RDI of CT were based on Hryniuk's model. RESULTS: The 5-year overall (OS) and cause-specific (CSS) survival was 39% and 51%, respectively, in patients who received CT+/-RT. Nine of the 14 patients who only received 1 cycle of CT died within 6 months from diagnosis without achieving complete remission (CR). However, the remaining 5 patients in this group survived 14-97+ months. Patients with a RDI >65% had a significantly better OS (p=0.029) and CSS (p=0.024) than those with a RDI 65%. Patients who received ABVD-based CT with a RDI >65% had a significantly better OS (p=0.0011) than those who were treated with ABVD-based CT with a RDI 65%, or MOPP-like therapy, irrespective of received RDI. INTERPRETATION AND CONCLUSIONS: Prognosis remains heterogeneous and the significance of established prognostic factors is limited in elderly HL patients. Patients who received a low RDI of CT and those receiving non-ABVD-based treatment fared worse. However, also elderly patients can enjoy long-standing complete remission following minimal treatment.

Parental longevity and survival in elderly patients with Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than younger patients. Factors such as inadequate therapy often due to decreased tolerance to treatment, presence of intercurrent diseases and accumulation of certain clinical and biological risk factors contribute to the poor outcome. Established predictors of prognosis in HL are less appropriate in the elderly population. Consequently, there is a need for additional markers to guide treatment decisions and to improve prediction of outcome. In the general population, the expected length of life of an individual is intimately associated with that of his/her parents. In a small cohort of elderly HL patients, we had previously observed high familial life-span of two previous generations predicts superior survival. The aim of this study was to test the hypothesis that parental longevity alone--an easily accessible and non-disease associated variable--is also associated with improved outcome using an enlarged series of elderly HL patients. DESIGN AND METHODS: One hundred and twenty-one patients with HL >60 years at diagnosis were included. The median follow-up time was 67 (range 37-175) months. Data regarding age at death and reported cause of death were available through parish offices for 228 (94%) parents. The effect of parental lifespan on HL survival included the use of Kaplan-Meier curves and Cox' proportional hazards regression analysis. RESULTS: Maternal as well as paternal lifespan correlated poorly with HL survival, both with regard to overall and disease-specific survival. There was, however, a tendency towards a decreased risk of dying among patients with low maternal lifespan (all-cause mortality: RR=0.7, 95% CI 0.5-1.0). INTERPRETATION AND CONCLUSIONS: Parental longevity does not predict superior survival in elderly patients with HL.

Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase--a report from the Swedish CML Group.

In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients < 65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders < 65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9; including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT; the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (< 65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.