Lymphoblastic leukaemia and non-Hodgkin's lymphoma

The outcome in childhood leukaemia has shown steady improvement over the last decade and efforts are now concentrated on the stratification of patients by risk factors which may avoid overtreatment of good risk patients and limit dose escalation strategies, including those with bone marrow transplantation, to the higher risk patients. In ALL, risk stratification is based on the presenting white cell count, sex, age and cytogenetics of the tumour cells. Even in acute myeloid leukaemia, the outcome with chemotherapy alone is now sufficient to limit elective allogeneic bone marrow transplantation to those who do not have cytogenetically favourable disease. In non-Hodgkins lymphoma, a dramatic improvement in overall survival from 50% to in excess of 80% has been achieved by an escalation in dose and dose intensity of chemotherapy. With this improvement, the prognostic influence of clinical staging has become less clear and recent efforts have concentrated on determining which groups of patients would be cured by less intensive treatment. As for ALL, there is concern about the potential late sequelae in these highly curable children. There remain groups of unusual tumour types, such as anaplastic large cell and peripheral T cell lymphoma, where there remains much to be learned about the pathogenesis and clinical behaviour. The optimum treatment strategy for these subgroups remains to be clarified.     

Microsatellite instability in follicle centre cell lymphoma

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.     

Microsatellite instability in B-cell lymphoma originating from Bloom syndrome

We present two cases of osteochondroma after total body irradiation in bone marrow recipients, the first in a 6-year-old boy with juvenile chronic myelogenous leukemia and the second in a 13-year-old boy with acute myelogenous leukemia. The patients developed multiple osteochondromas three years and seven years, respectively, after 12 Gy of total body irradiation. Neither had a family history of hereditary multiple osteochondromatosis. A review of the English literature revealed only one report describing five cases of osteochondroma after 12 Gy of total body irradiation in bone marrow transplant recipients. Osteochondroma should be considered as an additional adverse effect of total body irradiation.     

Clinical and laboratory features of adult T-cell leukaemia lymphoma in Barbados

We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in the other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.     

A role for growth hormone and prolactin in leukaemia and lymphoma?

Growth hormone (GH) and prolactin (PRL) quality as lymphohaemopoietic growth and differentiation factors, and so does insulin-like growth factor (IGF)-I, which mediates many of GH activities. Although there is only limited evidence that endocrine, paracrine or autocrine GH or PRL play a role in human leukaemia and lymphoma, the expression of these factors or their receptors may have diagnostic or therapeutic implications. Indeed, the participation of GH, PRL or IGF-I in the development or progression of certain haematological malignancies or to the antitumour immune response has been documented. Examples discussed in this review include a rat lymphoma in which the PRL receptor acts as an oncogene; the rat Nb2 lymphoma, which is dependent on PRL for growth; and experiments showing that PRL stimulates natural killer cell activity and the development of lymphokine-activated killer cells.     

Primary central nervous system lymphoma in a child with acute B-cell lymphoblastic leukaemia: consecutive Epstein-Barr virus-related malignancies

OBJECTIVE: The aim of the study was to evaluate the optimization of injection rates with an automatic power injector versus manual injection for contrast-enhanced breath-hold three-dimensional (3D) MR angiography of the abdominal aorta and its branches. SUBJECTS AND METHODS: In a prospective study, 50 patients underwent breath-hold 3D MR angiography (5/2 [TR/TE]; flip angle, 30 degrees) of the abdominal vessels on a 1.5-T system. Each patient received 0.15 mmol/kg of gadopentetate dimeglumine. All patients were randomly assigned to one of five equally sized groups. The contrast bolus was injected manually in group 1, always by the same investigator, who tried to perform a steady injection rate of 2 ml/sec. An automatic injector was used in groups 2-5 with injection flow rates of 0.5 ml/sec, 2 ml/sec, 4 ml/sec, and 6 ml/sec. The start of the MR sequence was tailored individually to the applied volume of contrast material after determination of circulation times by a test bolus. We measured the signal-to-noise and contrast-to-noise ratios as well as the relative vascular enhancement. The visualization of different abdominal vessel segments was independently ranked on a scale of 1-5 (1 = not visible; 5 = excellent visualization) by three reviewers who were unaware of the applied contrast material injection rate. RESULTS: The signal-to-noise and contrast-to-noise ratios of groups 3 and 4 (2 ml/sec and 4 ml/sec, respectively) were significantly (p < .05) higher than the ratios of groups 1, 2, and 5. The average relative vascular enhancement of groups 3 and 4 was significantly higher (p < .05) than the enhancement of all other groups. The contrast bolus applied with a faster injection rate (group 5) did not cover large parts of the K-space, resulting in increased blurring of the vessel contours. The subjective evaluation of large and small diameter vessels showed significantly better results in groups 3 and 4 than in groups 1, 2, and 5. CONCLUSION: The use of an automatic MR power injector proved superior to manual injection of contrast material. The optimal injection rate was 2 ml/sec for 3D breath-hold MR angiography of the abdominal vessels.     

Adult T cell leukaemia lymphoma in a non-aboriginal Australian woman with no apparent risk factors

OBJECTIVE: To present a case of adult T cell leukaemia lymphoma (ATLL) in a non-Aboriginal Australian woman with no apparent risk factor. CLINICAL FEATURES: A 43-year-old Australian woman of European descent presented with a febrile illness associated with generalised lymphadenopathy and splenomegaly. INVESTIGATIONS: There was lymphocytosis in the peripheral blood with a T helper cell phenotype. There were also lytic bone lesions with associated hypercalcaemia. HTLV-1 antibody was detected by agglutination assay and confirmed by western blot test. TREATMENT AND OUTCOME: After initial response to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), she relapsed and died with central nervous system involvement eight months after the initial diagnosis. CONCLUSION: To our knowledge this is only the third case of ATLL in a non-Aboriginal person in Australia.     

Endoscopic diagnosis of lower intestinal lesions of leukaemia and malignant lymphoma

There have been only a few endoscopic studies with respect to lower intestinal lesions of leukaemia and malignant lymphoma, although there have been many autopsy studies of these lesions. The aim of this study was to clarify these lesions using endoscopy. Colonoscopy was performed on 11 of 341 patients with leukaemia and on 32 of 105 patients with malignant lymphoma for frequent diarrhoea, anal bleeding or abnormal findings on barium enema examination, between April 1984 and September 1994. In eight of the 11 patients with leukaemia on whom endoscopy was performed, nine lesions were found; aphthoid ulcers, small ulcers or large tumours due to leukaemic infiltration were found in five, and colorectal adenoma was found in only one patient. Antibiotic-associated haemorrhagic colitis or pseudomembranous colitis was found in one patient each. In 10 of the 32 patients with malignant lymphoma, 11 lesions were found. The following were found in one patient each: large lymphomatous tumours, a large lymphomatous ulcer, multiple small polypoid lesions, multiple lymphomatous polyposis; and colorectal cancer or adenoma in six patients. However, the autopsy findings in patients with both diseases were mostly pseudomembrane formation or ulcers due to fungal and/or bacterial infection. It is concluded that accurate endoscopic diagnosis of lower intestinal lesions in patients with leukaemia or malignant lymphoma is essential for staging and treatment of these diseases and for determining their prognosis. Most lesions in leukaemia are aphthoid and small ulcers are due to leukaemic infiltration or antibiotics; most lesions in malignant lymphoma are elevated lesions such as cancer, adenoma or lymphomatous lesions as determined by endoscopy. This is in contrast to pseudomembrane formation or ulcers due to fungal and/or bacterial infection which are detected at autopsy.     

Inflammatory malignant fibrous histiocytoma: distinction from Hodgkin''s disease and non-Hodgkin''s lymphoma by a panel of leukocyte markers

The invariant chain (CD74) is preferentially localized in the cytoplasm and regulates the loading of exogenous derived peptides into HLA class II heterodimers. In addition, a small proportion of CD74:class II complexes is also expressed on the cell surface. We identified and quantified soluble CD74 (sCD74) molecules in the plasma and sCD74:sHLA-DR complexes by ELISA. EDTA plasma samples from 86 healthy probands were analyzed. sCD74 could be detected in all samples with a mean concentration of 1.14 relative units +/- 1.04 SD (range 0.17-4.31). Approximately 10% of the samples had increased amounts of sCD74 (>3.0 relative units). Complexes of sCD74 and sHLA-DR were detected in all samples and their quantities were positively correlated (r=0.83, p<0.001) with the sCD74 concentrations. SDS-PAGE analysis of plasma samples with high sCD74 concentrations (>3.0 relative units) revealed four isoforms of sCD74 with molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of intracellular CD74. However, only molecular weights of the 45 and 43 kDa isoforms of sCD74 are found complexed with sHLA-DR. Our data demonstrate, that CD74 molecules are present in their soluble form in the plasma of healthy probands and form complexes with soluble HLA-DR molecules.     

Clinical efficacy of ultrasound guided percutaneous drainage of abscesses in patients with leukaemia and lymphoma

Ultrasound guided percutaneous drainage (US-PD), a minimally invasive technique, has been reported as highly effective for the treatment of deeply located abscesses, particularly in immunocompromised patients. Therefore, we retrospectively studied its therapeutic efficacy and safety in a series of 14 patients with leukaemia and lymphoma. We collected the clinical and sonographic data of 14 patients with various types of leukaemia and lymphoma. These patients were consecutively observed in four clinical centres with long-term experience with ultrasound guided therapeutic techniques. The cases were analysed according to underlying disease, clinical features, location of the abscess, drainage technique, microbiological data and both short- and long-term outcome. In our series, 11 patients were treated with repeated ultrasound guided needle aspirations (US-NA) and 3 underwent catheter drainage (US-PCD). In 12/14 cases the procedure was successful (86%): the mortality rate was 14%. 5 patients died during the follow-up period because of the underlying disease, without abscess recurrence. No complications were reported. Our data suggest that ultrasound guided percutaneous drainage should be considered the first choice, minimally invasive procedure for the treatment of deeply located abscesses in patients with leukaemia and lymphoma.     

Relapsed lymphoblastic leukaemia in children: a continuing challenge

The basal bodies of green flagellates are often connected to striated microtubule-associated fibers (SMAFs), which are highly ordered bundles of 2 nm filaments. SF-assemblin (33 kDa) is the principal structural subunit of the SMAFs and consists of a non-helical head domain of approximately 32 residues and an alpha-helical rod domain that shows a pronounced coiled-coil forming ability. To investigate the functional role of the head domain we expressed N-terminally truncated molecules using a cDNA coding for SF-assemblin from Chlamydomonas reinhardtii. Recombinant wild-type SF-assemblin or molecules with an N-terminal deletion of ten residues formed striated fibers with an axial repeat of 28 nm. N-terminal truncations of 19 and 29 residues yielded assembly-incompetent molecules, revealing that the head domain is necessary for the constitution of striated fibers. Further, molecules with an internal deletion of 24 residues or with duplicated segments corresponding to insertions of 29 and 58 residues were constructed. The resulting fibers had altered cross-striation patterns and axial repeats. The observed shifts in the axial repeat corresponded well to the number of inserted or deleted residues, indicating a linear coherence between molecule length and axial repeat. The heptad pattern of the rod domain of SF-assemblin is regularly interrupted by skip residues. The removal of one or two skip residues had no significant effect on the ultrastructure of the striated fibers. Substitution of skip no. 2 with alanine resulted in a modified, asymmetric cross-striation pattern, indicating a polar architecture of the striated fibers. In summary, various mutations of SF-assemblin effected the solubility of the molecules, and the axial repeat, cross-striation pattern, or overall appearance of the fibers. Thus, analysis of SF-assemblin may represent a valuable system to study the interactions involved in the polymerization of fibrous coiled-coil proteins. A model of the SMAFs based on staggered protofilaments consisting of overlapping 36 nm subunits is presented.     

Cardiovascular risk reduction in a community setting: some comments

Four case reports are presented of patients who ate the meat of a hog inadvertently fed seed treated with fungicides containing ethyl mercury chloride. The clinical, electrophysiological, and toxicological, and in two of the patients the pathological data, showed that this organic mercury compound has a very high toxicity not only for the brain, but also for the spinal motoneurones, peripheral nerves, skeletal muscles, and myocardium.     

Can paternal preconceptional radiation account for the increase of leukaemia and non-Hodgkin's lymphoma in Seascale?

OBJECTIVE: To determine if the excess of leukaemia and non-Hodgkin's lymphoma in Seascale is restricted to those born in the parish and whether it might be explained by the postulated relation with paternal preconceptional radiation. DESIGN: Comparison, separately for those born in the parish and those born elsewhere, of the numbers of these malignancies observed in Seascale with those expected on the basis of reference rates for England and Wales. Details of paternal radiation levels were sought for each case. SETTING: The parish of Seascale in west Cumbria. SUBJECTS: Residents of Seascale below age 25 years in the years 1951-91. MAIN OUTCOME MEASURES: The observed and expected numbers of cases of leukaemia and non-Hodgkin's lymphoma within Seascale among those born there and among those born elsewhere. Also, the levels of any paternal preconceptional radiation associated with each case. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma at ages 0-24 was found in Seascale in those who were born there (ratio of observed to expected cases 8.6 and 20.2 respectively; p < 0.01). This also applied to those not born there (7.2 and 16.5; p < 0.01), a group often regarded as not showing an excess. The estimates were then conservatively recalculated so as to overestimate the risks among those born in Seascale and underestimate them among those born elsewhere. On this basis the six cases in those born in Seascale compare with 0.38 expected (15.8; p < 0.001), of which two were associated with paternal preconceptional life-time levels of 100 mSv or greater and three others with levels of 90-99 mSv. Among those born elsewhere, there were five cases (expected 0.74; ratio 6.7, p < 0.01), of which only one was associated with a high level of such radiation. CONCLUSIONS: Paternal preconceptional radiation cannot be the sole cause of the excess in Seascale since it will not explain the excess among those born outside Seascale. It follows that, unless two causes are to be postulated, any single cause must be a factor other than paternal preconceptional radiation. On this basis, the association found among those born there, if not partly due to chance, may reflect an indirect relation with the true cause. The recent hypothesis about such paternal radiation has originated in a subgroup of the excess cases that have aroused concern.     

Stage differences in the dependencies of topic initiation and topic following behavior.

I examined the topic initiation/topic following sequence data from the beginning, middle, and late stages of 16 counseling dyads (a successful and less successful dyad from each of eight counselors). I hypothesized that the beginning, middle, and end of successful counseling would demonstrate different patterns of dependency in the sequence data. Client and counselor topic initiation and topic following behavior was examined by using loglinear analysis to see the extent to which they varied because of the previous behavior of the other participant (interchain dependency), their own previous behavior (intrachain dependency), outcome (determined by a composite of client and counselor evaluations), and stage. Although high interchain dependencies were present for all the clients and counselors, significant variation was related to stage and outcome. Further, both clients and counselors in successful dyads demonstrated significant increases of intrachain dependency in the end stage, but no similar increases were found for either clients or counselors in the less successful dyads. These results are discussed with respect to relationship formation and development, differences in client and counselor role, and implications for future studies on interaction sequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interviews on a special topic: The profession of metallurgist yesterday,today, and tomorrow

Zaporozh'e. Translated from Metallurg, No. 1, pp. 7–9, January, 1992.