Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma.

We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.

A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (beta 67[E11] Val-Met->Asp).

The first reported case of congenital Heinz body hemolytic anemia was subsequently shown to be caused by an unstable hemoglobin, Hb Bristol [beta 67(E11) Val-Asp]. This has become one of the classic models of an unstable hemoglobin, the hydrophilic aspartate disrupting the hydrophobic heme pocket. We have restudied this original case, who remains clinically well after nearly 50 years of severe hemolysis with a hemoglobin level of about 7 g/dL and two unrelated Japanese cases. Surprisingly, all three cases show the same DNA changes, predicting a valine to methionine change at beta 67, rather than the expected aspartate. Further analysis with electrospray ionization mass spectrometry and globin chain biosynthesis strongly suggests that this anomaly is because of a novel posttranslational mechanism, with slow conversion of the translated methionine into an aspartate residue. The proximity of the heme and oxygen may be important in facilitating the reaction. These findings show the importance of complete characterization of variant hemoglobins using protein, DNA, and biosynthetic analyses.

The metabolites of nitric oxide in sickle-cell disease.

Plasma NOx concentrations were raised in 22 acute painful crises in SCD. We have measured blood concentrations of nitric oxide metabolites (NOx) in sickle-cell disease (SCD), and shown that they are increased compared with healthy controls (P = 0.002), and haemoglobin E/beta-thalassaemic controls (P = 0.05). Concentrations in steady-state SCD were also higher than in healthy controls (P = 0.04) but not significantly different from the concentrations at the beginning of painful crises (P = 0.34). Importantly, in 12 regularly exchanged sicklers, the mean pre-transfusion NOx concentration did not differ significantly from the control population (P = 0.52), suggesting that the changes in NO metabolism can be reversed. It is unlikely that the increased concentrations of NOx in SCD result from anaemia or haemolysis as the untransfused haemoglobin E/beta-thalassaemics did not show increased levels.

Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma.

Immediately before first hemi-body irradiation, 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance. 13 patients (22%) [8 of 31 (26%) controls, 5 of 28 (18%) in the interferon arm] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure. Mean time between upper and lower hemi-body irradiation was 69 days (range 35-294). Of 23 patients randomised to receive interferon and completing double hemi-body irradiation, 15 (65%) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days (61-241) from time of study entry. The mean period of interferon therapy, starting at a mean 65 days (26-160) post second hemi-body irradiation, is 16.4 months (2-33.5). There was no significant difference in median survival durations (10 months) from time of initial radiotherapy between control and interferon patients.

Pseudohyperkalaemia - a cause of diagnostic confusion.

Marked hyperkalaemia occurred on more than one occasion in 3 patients with thrombocytosis caused by the myeloproliferative syndrome. Initial failure to recognize that the elevation in the serum potassium level was an artefact resulted in unnecessary admissions to hospital and inappropriate investigations and treatment. Awareness of this entity and the use of suitable confirmatory tests should avoid such problems in management.

Agranulocytosis associated with carbamazepine, and a positive reaction with anti-lymphoid leukaemia antiserum during recovery.

Carbamazepine is a valuable drug in the treatment of trigeminal neuralgia and temporal lobe epilepsy. Rarely agranulocytosis has been described associated with its use but in this further non-fatal case a new finding of a positive reaction with anti-lymphoid leukaemia anti-serum was seen during the recovery phase. A brief review of 18 cases in the literature is provided and it is noted that 94% of reported cases are over the age of 45 years. The significance of the haematological finding is discussed.