Imatinib: a designer drug, another cutaneous complication.

A 55-year-old man with a history of mild psoriasis was started on imatinib for chronic myeloid leukaemia. He developed new nail dystrophy after treatment with an exacerbation of his psoriasis. Although not a contraindication for this drug, it should be remembered that psoriasis may worsen with imatinib.

Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival.

Eighty-four patients with typical chronic lymphocytic leukemia (CLL) (by morphological and immunophenotypic criteria) on whom karyotypes were available were studied. Binet stage at diagnosis and follow-up were defined. Survival was calculated from diagnosis. Fifty-one percent of patients had a karyotypic abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different survival from patients with normal karyotype. The second commonest abnormality was del(11q) (13%); these patients had significantly worse survival when compared both with patients with normal karyotype (P < 0.0001) and with other patients with karyotypic abnormality (P = 0.0012). All patients with del(11q) had progressed to stage C at follow-up while only 20% of the other patients had shown any disease progression (P < 0.0001). Del(11q) may identify a subset of patients with typical CLL who have worse survival and consistent disease progression and in future may help define a group of patients with CLL who could benefit from earlier or more intensive therapy.

Engraftment characteristics of peripheral blood stem cells mobilised with cyclophosphamide and the delayed addition of G-CSF.

The optimal protocol for the mobilisation of PBSC remains unknown. We present data on 42 patients mobilised with cyclophosphamide (3 or 4 g/m2) and the delayed addition of a standard 300 micrograms dose of G-CSF (Filgrastim) from day +5. The patients had received a median of 2 previous chemotherapy regimes, 38% had received prior radiotherapy and 38/42 had active disease at the time of mobilisation. The protocol was well tolerated and 38 patients proceeded to transplantation. The median number of CD34+ cells reinfused was 4.3 x 10(6)/kg (range 0.5-30) and CFU-GM 15.8 x 10(4)/kg (range 0-148). The total number of CD34+ cells harvested correlated with the total number of CFU-GM available for reinfusion (P = 0.008). Overall engraftment occurred within median days to neutrophils > 0.5 x 10(9)f/l or platelets > 20 x 10(9)/l of 14 and 13 days, respectively. Patients receiving more than 2.5 x 10(6)/kg CD34+ cells had even more rapid haemopoietic reconstitution with significant reductions in hospital stay and transfusion requirements. Those below this threshold had significantly delayed platelet engraftment. The mobilising dose of cyclophosphamide did not influence the achievement of the threshold CD34+ cell yield for optimal engraftment. The delayed addition of a standard 300 micrograms G-CSF dose after priming chemotherapy resulted in the use of a median 9 days hence 9 vials of G-CSF. This protocol presents the potential for cost saving without compromising the quality or success of PBSC mobilisation.

Adjuvant alpha-interferon improves complete remission rates following allogeneic transplantation for multiple myeloma.

Allogeneic transplantation may be curative in a proportion of patients with multiple myeloma (MM), but relapse is a major cause of treatment failure. We sought to improve complete remission (CR) rates by the use of alpha-interferon (alpha-IFN) in patients not in CR when evaluated 4 months post-transplant. We report five of 13 evaluable patients undergoing allogeneic sibling BM or PBSC transplantation for MM between 1990 and 1997 who met the criteria for adjuvant alpha-IFN therapy. A starting dose of 3 MU x 3/week was commenced at median time of day +126 (range day +112-224) post-transplant and was well-tolerated. In contrast to other reports we observed no increased toxicity in terms of GVHD compared to those patients not receiving alpha-IFN therapy and only one patient treated with alpha-IFN has developed chronic GVHD. Durable CRs were achieved in two patients within 8 weeks of starting therapy whilst two other patients required a longer course of alpha-IFN to achieve CR (36 weeks and 30 weeks, respectively). One patient whose paraprotein was rapidly rising at the time of alpha-IFN therapy clinically relapsed despite 6 months of treatment. None of the patients who achieved CR following alpha-IFN therapy have relapsed and we conclude that alpha-IFN is a safe and effective adjuvant treatment for some patients in the achievement of CR following allogeneic transplantation for myeloma.

Enterococcal meningitis in an HIV positive haemophilic patient.

A 25 year old, human immunodeficiency virus (HIV) seropositive, severe haemophilic patient was treated for suspected Pneumocystis carinii infection with high dose intravenous cotrimoxazole and subsequently with prednisolone. When he improved he was discharged on oral treatment only to return two days later, extremely unwell, with headaches, fever, sweats, tachycardia and hypotension. A lumbar puncture showed modest neutrophil pleocytosis but despite empirical antibiotic treatment with intravenous benzylpenicillin and cefuroxime he continued to deteriorate. Culture of cerebrospinal fluid subsequently grew Enterococcus faecalis that was resistant to trimethoprim and sensitive to ampicillin, rifampicin, and vancomycin. After a change in treatment to intravenous ampicillin and rifampicin he dramatically improved. Enterococcal meningitis is rare in adults but important to recognise and treat appropriately in view of its high mortality and relative resistance to antibiotics. In our case the combination of HIV infection and previous treatment with antibiotics or steroids, or both, were probable predisposing factors.

Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia.

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.

Trisomy 12 in B-cell chronic lymphocytic leukaemia: an evaluation of 33 patients by direct fluorescence in situ hybridization (FISH).

An adaptation of the standard fluorescence in situ hybridization (FISH) technique allowing rapid analysis (4 h) has been used to study the prevalence of trisomy 12 in 33 patients with B-CLL, of whom 54% have been shown to have this abnormality. The presence of trisomy 12 has been compared with clinical parameters, and there may be a relationship between the prevalence of trisomy 12 in B-CLL and duration of disease.

The sequential analysis of trisomy 12 in B-cell chronic lymphocytic leukaemia.

In this longitudinal study we evaluated the clinical significance of screening for trisomy 12 by fluorescence in situ hybridization (FISH) and correlated these findings with survival, disease progression and need for treatment. Interphase FISH was performed on 85 patients in 1993/94 and repeated on 41 patients in 1996/97. Over the 4-year period there was no significant change in the percentage of trisomic cells, even in patients with disease progression. Overall survival and requirement for treatment were similar for patients with and without FISH-defined trisomy 12.