Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

Translocations t(14;18) and t(8;14) with rearranged bcl-2 and c-myc in a case presenting as B-ALL (L3).

Follicular lymphoma is a low grade malignancy characterized by the translocation t(14;18), which involves the putative oncogene bcl-2. We describe a 73-year-old patient presenting with Burkitt acute lymphoblastic leukemia (B-ALL) L3 (Burkitt type), whose cells had the following immunophenotype: CD19+, CD22+, HLA-DR+, CD10+, TdT-, Cyt IgM-, CD34-. Analysis of 25 peripheral blood metaphases showed the presence of t(14;18) (q32;q21), and t(8;14) (q24;q32) in 24 cells and t(14;18) only in one cell, suggesting that the latter translocation came first during clonal evolution. Both bcl-2 and c-myc were rearranged in addition to the immunoglobulin heavy and light chain genes. The presence of small lymphoid cells in paratrabecular areas on the bone marrow biopsy, together with evidence of cytogenetic clonal evolution, was indicative of a transformation from a low grade follicular lymphoma to a more aggressive Burkitt type malignancy.

Bone marrow transplantation for severe aplastic anaemia using cyclosporin: long-term follow-up.

Between 1980 and 1986 we transplanted 49 patients from genotypically identical sibling donors for severe aplastic anaemia (SAA). Patients were predominantly adults, median age 22 years (3-47). Forty-six were multiply transfused prior to referral. The median pre-transplant disease duration was 4 months (1-72). Pre-transplant conditioning was with cyclophosphamide (CY) 200 mg/kg. Cyclosporin A (CSA) was given from 1 day before the transplant and continued for 9-12 months. Eight of 48 evaluable patients did not achieve initial engraftment (early graft failure). Six of these episodes occurred in the eight cases transplanted more than 1 year after diagnosis, four of whom died. Thirteen of 44 (30%) evaluable patients (with stable engraftment after one or two transplants) had grade III-IV acute graft-versus-host disease (GVHD). Only three of 35 patients surviving more than 100 days with sustained engraftment developed generalized chronic GVHD; two died. An additional 10 patients developed localized chronic GVHD, which was very mild, transient and related to CSA withdrawal. Four long-term survivors are known to have autologous marrow function. All survivors have Karnofsky scores of greater than 90%. We conclude that the use of CSA after bone marrow transplantation for SAA is associated with good long-term survival and minimal on-going chronic GVHD. Early graft failure was frequent when transplantation was delayed beyond 1 year from diagnosis.

Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity.

Sixty-four patients with aplastic anemia were treated with antilymphocyte globulin (ALG Merieux) between 1980 and 1985. The actuarial survival for all patients was 53% at 6 years, with 79% survival for nonsevere aplastic anemia (NSAA) and 36% for severe aplastic anemia (SAA). The neutrophil and platelet counts before treatment with ALG were highly predictive of survival, whereas sex, age, and etiology were not. Duration of disease prior to ALG treatment was inversely related to survival, although this was not statistically significant. Survival was closely associated with response to ALG, especially for patients with SAA. The response to one course of ALG was 33%. Eighteen patients who did not respond to an initial course of ALG received a second course; of these, four (22%) responded. The overall response to one or two courses of ALG was 40%. The mean RBC volume (MCV) measured after ALG treatment was a useful early indicator of response. Both the minimum lymphocyte count during ALG therapy and the mean lymphocyte count after therapy, however, were not significantly different between responders and nonresponders. The disappointing survival of patients with SAA in this study may reflect the poor clinical condition of severely affected patients referred to us and/or the presence of longstanding aplasia. The importance of studying a large series of patients with long-term follow-up to assess ALG in the treatment of aplastic anemia is shown by this investigation.

Primary plasma cell leukaemia: immunological and ultrastructural studies in 6 cases.

The clinical and laboratory studies of 6 patients with primary plasma cell leukaemia are described. The leukaemic cells had a variable morphology, ranging from lymphoplasmacytic and mature plasma cells to poorly differentiated blasts. The neoplastic plasma cells had a characteristic phenotype: they were positive for CyIg and the McAb OKT10 and Ri-3, and did not express the B-cell antigens Ia, B1 and B4. Ultrastructural studies confirmed the plasma cell nature of the leukaemic cells and showed the presence of a meshwork of cytoplasmic fibrils in 50 to 90% of the neoplastic cells from all cases. The distinct ultrastructural and immunological features of PCL described in this study will help the diagnosis and further characterisation of this disease entity.

Treatment of aplastic anaemia with antilymphocyte globulin (ALG).

Thirty-one patients with aplastic anaemia were treated with antilymphocyte globulin (ALG) followed by anabolic steroids. All patients were reviewed at least 1 year after receiving treatment. Twenty-one patients were considered to have a severe form of aplasia. ALG from three sources was used during the trial. Sixteen patients were alive at the time of analysis, eight who had had severe aplastic anaemia (38%) and five of these no longer require blood support. No difference in response was found according to type of ALG used. Patients with a long history of aplasia before treatment fared worse than those with a short history. These results were better than those obtained with anabolic steroids alone in historical controls. It is concluded that ALG treatment is worth giving to patients with aplastic anaemia but that the optimum way of giving this immunosuppression may be different from that used in this presentation.

Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A.

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.

Regeneration of peripheral blood cells following allogeneic bone marrow transplantation for severe aplastic anaemia.

We have studied the pattern of regeneration of peripheral blood cells following ABO compatible bone marrow transplantation for severe aplastic anaemia. 18 patients were treated with cyclosporin A and six with methotrexate for post graft immunosuppression. The number of days taken for the neutrophil count to reach 0.5 x 10(9)/l, the lymphocyte count to reach 1.0 x 10(9)/l, the platelet count to reach 100 x 10(9)/l and the reticulocytes to reach 1% was shorter in the CyA treated patients. This finding reached statistical significance for all types of cells except the platelets (neutrophils, P less than 0.001; lymphocytes, P less than 0.02; platelets, P greater than 0.05; reticulocytes, P less than 0.001). The more rapid regeneration of peripheral blood cells in patients treated with cyclosporin A has contributed to reducing the length of time patients are dependent on blood product support in the post transplant period.

Bone-marrow transplantation for severe aplastic anaemia using histocompatible unrelated volunteer donors.

Two patients with severe aplastic anaemia received bone-marrow transplants from unrelated donors selected for HLA compatibility. Graft-versus-host disease occurred in both patients but responded to treatment. Both patients had stormy courses after grafting, but subsequently their conditions improved, and one was not receiving any treatment at follow-up after day 330 while the other had mild chronic graft-versus-host disease at day 150. These results show that unrelated, histocompatible volunteers may successfully donate marrow for the treatment of severe aplastic anaemia, though many problems remain to be solved.

Effects of high dose busulphan on leukaemic progenitor cells in chronic myeloid leukaemia.

Six patients with Philadelphia positive chronic myeloid leukaemia (CML) were treated with single high doses of busulphan. The action of busulphan on the in vivo kinetics of circulating progenitor cells (colony forming cells) was measured using an agar culture system which involved scoring of total colonies and clusters at 7 days and of granulocyte, monocyte and eosinophil colonies at 14 days. High dose busulphan was found to be effective in suppressing circulating granulocyte, monocyte and eosinophil progenitor cells. The effect of busulphan on progenitor cells was rapid and their levels fell by at least 85% within five days. By contrast, the white blood cells fell by only 9% and the platelets fell by 10% over this time. Subsequently, the white cell count and platelet count fell to near normal levels. The progenitor cell levels began to rise again at a mean of 35 days following busulphan treatment and the white blood cells at a mean of 39 days in four patients. One patient remained in haematological remission for six months following 100 mg of busulphan with less than 1 progenitor per 5 x 10(5) peripheral blood nucleated cells. One patient in myeloblastic transformation had a previously not described culture pattern consisting of a high cluster to colony ratio at 7 days and of an increased number of predominantly eosinophilic colonies at 14 days. There was no significant fall in progenitor cell levels following busulphan and this patient died.