Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis.

BACKGROUND: Central vein catheters, which are used in the treatment of cancer patients, are prone to thrombotic complications of the catheter or adjacent vein. Previous studies suggest that 1 mg warfarin daily (minidose) can significantly reduce that risk. AIMS: This, study aims to establish whether minidose warfarin could reduce catheter-related thrombosis in adult patients with haematological malignancies. METHODS: Patients were randomly selected to receive warfarin or not. The end-points studied were: (i) occlusion by thrombus, (ii) removal of catheter for other reasons or (iii) 90 days free of thrombus. RESULTS: There was no significant difference in the incidence of catheter thrombosis or venous thrombosis and no significant variation in catheter survival between the study and control groups. CONCLUSIONS: This study found no benefit of the routine use of minidose warfarin for prophylaxis of central vein' catheter thrombosis in patients with haematological malignancies and therefore does not support the routine use of minidose warfarin for prophylaxis in such patients.

Trisomy 10 in acute myeloid leukemia: three new cases.

Trisomy 10 is a rare nonrandom cytogenetic abnormality found in association with acute myeloid leukemia (AML). The hematological and clinical features associated with this finding have not yet been clearly defined. A literature review revealed 13 cases of trisomy 10 in AML, some reported as a minority component of a more comprehensive AML study and therefore lacking a full description of both clinical and hematological features. We present a summary of these reports and add three new cases to the literature.

Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis.

Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy.

Iliopsoas haemophiliac pseudotumours with bowel fistulation.

Two cases of iliopsoas haemophilic pseudotumours are presented. In one patient a fistula developed between a pseudotumour and the large bowel. This resulted in an abscess involving the pseudotumour and adjacent tissues. It resolved after 5 years of therapy involving percutaneous drainage and closure of the fistula. The second patient had a massive pseudotumour that had obstructed both ureters. Later he suffered a fatal mixed Gram negative septicaemia probably related to erosion into the colon.

Characterization of the C-MYC amplicon in a case of acute myeloid leukemia with double minute chromosomes.

We have characterized the double minute chromosomes in a case of acute myeloid leukemia (AML). Southern blot analysis showed that the C-MYC was amplified. Further analysis with probes located both 3' and 5' of MYC indicated that the amplicon was at least 700 kb in size, extending from the papilloma virus integration site situated 500 kb 5' of MYC to the PVT gene located 280 kb 3' of MYC. This appears to be the largest MYC-containing amplicon in human leukemia.

Electrospray ionization mass spectrometry identification of fibrinogen Banks Peninsula (gamma280Tyr-->Cys): a new variant with defective polymerization.

Fibrinogen Banks Peninsula was identified in the mother of a patient referred for investigation following recurrent epistaxis. Coagulation tests revealed prolonged thrombin and reptilase times and a decreased functional fibrinogen level. Thrombin-catalysed release of fibrinopeptides A and B was normal, and no abnormalities were detected by DNA sequencing of the regions encoding the thrombin cleavage sites in the Aalpha and Bbeta genes. Reducing SDS-PAGE and reverse-phase HPLC analysis of purified fibrinogen chains were normal, as was electrospray ionization mass spectrometry (ESI-MS) analysis of isolated Aalpha and Bbeta chains. However ESI-MS revealed a mass of 48345 D for the isolated gamma chains, 31 D less than the measured mass of control chains (48376 D). Since normal and abnormal gamma chains were not resolved, this implies a 60-62 D mass decrease in 50% of the molecules. A 60 D decrease was confirmed when DNA sequencing indicated heterozygosity for a mutation of Tyr-->Cys at codon 280 of the gamma chain gene. Fibrin monomer polymerization revealed a delayed lag phase and reduced final turbidity and although factor XIIIa crosslinking of fibrinogen was normal, it is likely that this delay is due to impaired D:D self association. Recent crystallographic studies show residues gamma280 and gamma275 make contact across the D:D interface, suggesting a similar mechanism for the polymerization defects in fibrinogens Banks Peninsula and Tokyo II (gamma275Arg-->Cys).

Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism.

BACKGROUND: A study was undertaken to assess the usefulness of the SimpliRED D-dimer test, arterial oxygen tension, and respiratory rate measurement for excluding pulmonary embolism (PE) and venous thromboembolism (VTE). METHODS: Lung scans were performed in 517 consecutive medical inpatients with suspected acute PE over a one year period. Predetermined end points for objectively diagnosed PE in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary angiogram, (3) a high probability ventilation perfusion lung scan when the pretest probability was also high, and (4) the unanimous opinion of an adjudication committee. Deep vein thrombosis (DVT) was diagnosed by standard ultrasound and venography. RESULTS: A total of 40 cases of PE and 37 cases of DVT were objectively diagnosed. The predictive value of a negative SimpliRED test for excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO2 of > or = 80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory rate of < or = 20/min was 0.95 (error rate 14/308). The best combination of findings for excluding PE was a negative SimpliRED test and PaO2 > or = 80 mm Hg, which gave a predictive value of 1.0 (error rate 0/93). The predictive value of a negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249). CONCLUSIONS: All three of these observations are helpful in excluding PE. When any two parameters were normal, PE was very unlikely. In patients with a negative SimpliRED test and PaO2 of > or = 80 mm Hg a lung scan is usually unnecessary. Application of this approach for triage in the preliminary assessment of suspected PE could lead to a reduced rate of false positive diagnoses and considerable resource savings.

Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity.

Transfer of donor immunity has been demonstrated in animal models of both allogeneic and syngeneic bone marrow transplantation (BMT). Clinical case reports have suggested that human autoimmune disease may be similarly transferred. However, it is difficult to completely exclude autoimmune phenomena associated with graft-versus-host disease (GVHD) as previously reported cases are of allogeneic BMT. In addition, the onset of autoimmunity has been distantly related to the timing of the transplant, perhaps because of the immunosuppression used for prophylaxis and treatment of GVHD. We describe a patient in whom the development of psoriasis shortly after receiving syngeneic bone marrow from a psoriatic donor and its recurrence with arthropathy following a second syngeneic BMT provide more direct evidence for the adoptive transfer of human autoimmune disease, probably by T cells.

De novo mutation of the platelet glycoprotein Ib alpha gene in a patient with pseudo-von Willebrand disease.

Pseudo (or platelet-type)- von Willebrand disease (vWD) is a very rare autosomal dominant bleeding disorder caused by an abnormal hyper-responsiveness of the platelet membrane glycoprotein (GP) Ib/IX complex, the receptor for von Willebrand factor. We found a heterozygous missense mutation in the GPIb alpha gene in a sporadic case with pseudo-vWD: Met (ATG) to Val (GTG) at residue 239. The mutation was not detected in either parent. Investigation of three variable number of tandem repeat loci, D1S80 (MCT118), vWA and D17S5 (YNZ22), confirmed paternity and the de novo origin of the mutation. Furthermore, we have shown by the TaqI polymorphism analysis, which is located downstream of the GPIb alpha gene, that the mutation occurred in the maternal allele. This is the first description of de novo mutation occurred in pseudo-vWD and/or platelet GPIb alpha gene.

Acquired heparin-like anticoagulants: a second case in metastatic breast carcinoma and literature review.

We report the second case of an acquired heparin-like anticoagulant in a patient with disseminated breast carcinoma. All but one of the small numbers of other cases have also been associated with an underlying malignancy. We comment on the distinction between an immunoglobulin and proteoglycan causing the antithrombin effect and suggest points of interest for consideration in any future cases together with a review of treatment options.

Cloning and sequencing of a t(14;19) breakpoint that involves the C mu switch region.

The t(14;19) is a recurring translocation found in a small number of cases of chronic B-cell leukemia (CLL). We have cloned and sequenced the breakpoint in a patient with a t(14;19) and shown that the breakpoint on chromosome 14 occurred in the C mu switch region, and that the breakpoint on chromosome 19 occurred in the 5' untranslated region of the BCL3 gene. This is in contrast to all the other reported cases with a t(14;19) in which the breakpoints on chromosome 14 occurred in the C alpha 1 or C alpha 2 switch region, and the breakpoints on chromosome 19 occurred upstream of the BCL3 gene. Our results further emphasize the importance of the switch region in the t(14;19) translocation.

Complex karyotypic evolution in B-cell chronic lymphocytic leukemia.

Cytogenetic analysis at diagnosis in a female patient with chronic B-cell leukemia showed a single abnormal clone with a 4p+ abnormality, 46,XX, -4, +der(4)t(4;?)(p16;?). Six additional clones evolved from this clone during the following 4 1/2 years and showed 3p+, 4p-, and 11q- chromosomes in addition to the 4p+ abnormality. Immunoglobulin heavy chain gene rearrangement studies showed two rearranged bands and a faint germline band. Following splenectomy, a strong germline and faint rearranged bands were seen, suggesting that the majority of cells were normal, whereas cytogenetic studies showed that the karyotypically abnormal cells were still present. The combination of cytogenetic and Ig gene rearrangement studies provides detailed information regarding the number of circulating normal and leukemic cells.

Aplastic anaemia in Christchurch Hospital 1979-89.

We have reviewed the records of all patients referred to our departments with aplastic anaemia during the 11 years from 1979 to 1989. Of the 22 patients identified, 19 fulfilled the standard criteria for severe aplastic anaemia. There were 11 females and 11 males. Their mean age was 35 (range 2-85 years). Five cases followed exposure to drugs known to cause aplastic anaemia and one had a recent history of viral hepatitis. A variety of treatments were used. Four patients received an allogeneic bone marrow transplant (BMT) from matched sibling donors and two of these were alive and well 65 and 120 months post BMT. Antithymocyte globulin (ATG) treatment has been followed by lasting complete remission in two of the six patients treated and a partial response was seen in one other patient. Cyclosporin therapy was associated with unmaintained complete remission in one of the three patients given this drug after ATG had failed. The remaining 13 patients received only supportive care with or without androgens and six (46%) had early recovery of bone marrow function with lasting complete remission. These patients illustrate some of the therapeutic options available for aplastic anaemia.

The costs and benefits of bone marrow transplantation.

The average direct costs of performing a bone marrow transplant (BMT), including the subsequent year, was found to be NZ$27,074 for 43 consecutive transplants. In 29 BMTs a full two year period of follow up was available and a quality of life analysis was carried out on these patients. It was calculated that 59 quality adjusted life years (QALYs) had been gained by the BMT procedure at the time of analysis. By combining these two analyses the cost of each QALY gained by BMT is NZ$13,272. The relatively low cost of BMT is partly due to the extremely low annual costs in second and subsequent years post BMT. In our patients this cost amounted to $195 per year. The costs and benefits of BMT compare very favourably with other complex medical procedures.

Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients.

PURPOSE: To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODS: Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS: Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION: Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration.

Busulphan/cyclophosphamide conditioning for bone marrow transplantation may lead to failure of hair regrowth.

Following the introduction of bulsulphan and cyclophosphamide (BUCY) conditioning in our unit in 1987, a number of patients noted incomplete scalp hair regrowth following bone marrow transplantation (BMT). Between August 1987 and May 1989, 22 patients had undergone allogeneic or autologous BMT in our unit and we recalled for detailed assessment the 14 who were alive and well at least 6 months post grafting. Six patients had experienced incomplete hair regrowth of varying severity 7-27 months following BMT. All those affected had received BUCY conditioning and the four most severely affected were allogeneic BMT recipients. No patient had received any post-BMT chemotherapy or radiation. None of the patients had evidence of graft-versus-host disease. No laboratory test abnormalities distinguished the affected from the unaffected patients. Despite the relatively small number of patients, our results suggest that BUCY has caused permanent damage to the hair follicles of the affected patients. Prolonged alopecia may markedly impair the quality of life for long-term survivors of BMT and this unexpected complication also has significant medicolegal implications.