Long-term follow-up of aplastic anaemia.

Of 61 patients with aplastic anaemia (AA) diagnosed in our hospitals, 37 survived more than 2 years; actuarial survival of this latter group was 58%, with a median follow-up of living patients of 10.2 years. Laboratory and clinical data pertaining to these long-term survivors was scrutinized to determine the incidence of clonal disorders, which was identified in 43%. Morphological evidence of the myelodysplastic syndrome (MDS) was found in 13 (35%), including four cases of RAEB; four (11%) developed PNH. Of 23 patients studied, four showed karyotypic abnormalities, but these did not always coincide with morphological features of MDS. Although four patients now have completely normal blood and marrow morphology, and another had normal blood and marrow morphology at the time of death due to unrelated disease, the study confirms the high incidence of cytopenia and morphological abnormality, sufficient to justify a diagnosis of MDS, in patients with a history of AA. No definite survival plateau was identified. However, the natural history of MDS secondary to AA seems to be different to that of MDS arising de novo; the clinical course is relatively indolent, possibly implying a different biology.

Acute lymphoblastic leukaemia following Hodgkin's disease is associated with a good prognosis.

Acute leukaemia, both myeloid and lymphoblastic, in patients treated for Hodgkin's disease (HD) is thought to have a poor prognosis. We report four adults who developed secondary acute lymphoblastic leukaemia (ALL) following chemoradiotherapy for HD. The chromosomal translocation t(4;11) (q21;q23) was found in two patients who received a chemotherapeutic regimen containing the DNA topoisomerase II inhibitor etoposide. Three of the four patients are alive and in unmaintained first remission at 3, 5 and 9 years from diagnosis of ALL, two following autologous bone marrow transplantation. These results suggest that ALL following HD may have a good prognosis when treated aggressively.

Three cases of the myelodysplastic syndrome with pericentric inversion of chromosome 16.

Inversion of chromosome 16, inv(16)(p13q22), is characteristic of acute myeloid leukaemia (AML) with eosinophilia and is rarely found in the myelodysplastic syndrome (MDS). We report three cases of MDS in which inv(16) was observed. They were classified to FAB subtypes RA, RARS and RAEBT; eosinophilia or abnormal eosinophils were not observed. The disease appeared to be stable in all three patients. MDS with inv(16) without eosinophilia may be a rare subgroup associated with a good prognosis.

A genetic algorithm to improve a neural network to predict a patient's response to warfarin.

The ability of neural networks to predict the international normalised ratio (INR) for patients treated with Warfarin was investigated. Neural networks were obtained by using all the predictor variables in the neural network, or by using a genetic algorithm to select an optimal subset of predictor variables in a neural network. The use of a genetic algorithm gave a marked and significant improvement in the prediction of the INR in two of the three cases investigated. The mean error in these cases, typically, reduced from 1.02 +/- 0.29 to 0.28 +/- 0.25 (paired t-test, t = -4.71, p < 0.001, n = 30). The use of a genetic algorithm with Warfarin data offers a significant enhancement of the predictive ability of a neural network with Warfarin data, identifies significant predictor variables, reduces the size of the neural network and thus the speed at which the reduced network can be trained, and reduces the sensitivity of a network to over-training.

Dietary deficiency of vitamin B12 is associated with low serum cobalamin levels in non-vegetarians.

A prospective study of 106 patients with low serum cobalamin (vitamin B12) levels showed that, in 37, it was unexplained. The dietary intake of the vitamin was assessed in these patients by questionnaire and was found to be low in 10 (37%). None of these patients was vegetarian and they were of varying age and social circumstance. Dietary deficiency may be the sole cause of a low serum cobalamin in a significant proportion of non-vegetarians. An assessment of dietary intake should be part of the investigation of cobalamin deficiency.

Failure of mithramycin to control the myeloid blast phase of chronic granulocytic leukemia: a report on nine patients and review of the literature.

After reports of the successful use of mithramycin and hydroxyurea in the myeloid blast phase of chronic granulocytic leukemia, we treated nine patients according to the protocol devised by Koller and Miller (1986). There were no complete responses, but one patient had a partial response with a transient return to the chronic phase. Of the remaining eight patients, two experienced lessening of bone pains, and one a reduction in spleen size, but without hematological improvement. The regimen was associated with significant toxicity, and no overall survival advantage. We present a review of published data regarding the use of mithramycin in chronic granulocytic leukemia which supports the results in our series. The combination of mithramycin and hydroxyurea is largely ineffective in the blast phase of chronic granulocytic leukemia, but may be of value in the accelerated phase.

Portal hypertension and ascites in systemic mastocytosis.

We report a case of systemic mastocytosis (SM) presenting as ascites and portal hypertension. The haematological picture at presentation was suggestive of chronic myelomonocytic leukaemia. Initial difficulties in making a diagnosis of SM were encountered as the cutaneous signs were atypical. The correct diagnosis was established only after tissue sections were appropriately stained for mast cells. The liver biopsy showed portal and sinusoidal mast cell infiltration, portal fibrosis and evidence of hepatic venous outflow obstruction. The disease progressed rapidly and recurrent massive ascites was a dominant problem. This case illustrates again the problems of making a diagnosis of SM especially when the clinical picture is atypical. Ascites as a presenting manifestation of SM has been reported previously in only six patients. Published cases of SM with portal hypertension or ascites or both are reviewed.