High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H.

T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. This study reports results in 39 patients with T-PLL treated with CAMPATH-1H between March 1993 and May 2000. All but 2 patients had received prior therapy with a variety of agents, including 30 with pentostatin; none achieved complete remission (CR). CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). Survival was significantly prolonged in patients achieving CR compared to PR or no response (NR), including one patient who survived 54 months. Nine patients remain alive up to 29 months after completing therapy. Seven patients received high-dose therapy with autologous stem cell support, 3 of whom remain alive in CR 5, 7, and 15 months after autograft. Stem cell harvests in these patients were uncontaminated with T-PLL cells as demonstrated by dual-color flow cytometry and polymerase chain reaction. Four patients had allogeneic stem cell transplants, 3 from siblings and 1 from a matched unrelated donor. Two had nonmyeloablative conditioning. Three are alive in CR up to 24 months after allograft. The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. The use of stem cell transplantation to consolidate responses merits further study.

Linkage analysis for major histocompatibility complex-related genetic susceptibility in familial chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) shows evidence of familial aggregation, but the genetic basis is poorly understood. The existence of a linkage between HLA and Hodgkin lymphoma, another B-cell disorder, coupled with the fact that CLL is frequently associated with autoimmune disease, led to the question of whether the major histocompatibility complex (MHC) region is involved in familial cases of CLL. To examine this proposition, 5 microsatellite markers on chromosome 6p21.3 were typed in 28 families with CLL, 4 families with CLL in association with other lymphoproliferative disorders, and 1 family with splenic lymphoma with villous lymphocytes. There was no evidence of linkage in these families to chromosome 6p21.3. The best estimates of the proportions of sibling pairs with CLL that share 0, 1, or 2 MHC haplotypes were not significantly different from the null expectation. This implies that genes within the MHC region are unlikely to be the major determinants of familial CLL. (Blood. 2000;96:3982-3984)

A case of haemophagocytic syndrome and Kikuchi-Fujimoto disease occurring concurrently in a 17-year-old female.

An unusual case in which a young Asian female presenting with fever, lymphadenopathy and cytopaenia was found to have distinct histological features of both haemophagocytic syndrome (HS) and histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease, KFD) is presented. We review the clinical features of each of these rare, but important, diagnoses and propose the hypothesis that they may form part of a disease continuum, rather than representing separate entities.

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia.

Nineteen patients with high-risk myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) received fludarabine, cytarabine, granulocyte-colony stimulating factor (G-CSF), and idarubicin chemotherapy (de novo MDS/MDS-AML, nine; relapsed/refractory MDS/AML, seven; therapy-related MDS, three). Median age was 44 years and median disease duration 10 months. 16/19 (84%) patients had abnormal cytogenetics with seven (37%) harbouring abnormalities of chromosome 7. 18/19 (94.7%) patients responded to FLAG-idarubicin with 12 (63%) achieving complete remission (CR) (< 5% blasts and normal cytogenetics). 7/9 (78%) patients with de novo MDS/MDS-AML achieved CR compared to 5/10 (50%) with alternative diagnoses. Response was associated with age < 50 years, disease duration < 3 months, and cytogenetics other than abnormalities of chromosome 7. Haemopoietic regeneration was rapid in most patients and there were no toxic deaths. Nine patients received a second course of chemotherapy, three have proceeded to allogeneic bone marrow transplant and three to autologous blood stem cell/bone marrow transplantation. Follow-up is short (median 10 months). 12/19 (63%) patients remain alive and 5/12 (42%) have relapsed at a median 5 months following CR achievement. FLAG-idarubicin was well tolerated. High rates of morphological and cytogenetic remission, especially in de novo MDS, offer a window of opportunity for assessment of autologous BMT in this group of diseases where no treatment except alloBMT has led to prolongation of survival.

Idarubicin for remission induction of acute myeloid leukemia: United Kingdom multicenter experience.

Ninety-eight adult patients with acute myeloid leukemia were given variable remission induction/consolidation regimens containing idarubicin. Sixty-nine (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24) or had primary refractory disease (n = 5) (median age, 46 years). Complete remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed patients, with no difference for those below or above 55 years of age (56% v 59%) or for patients exhibiting white blood cell counts of less or more than 50 x 10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of the total number of patients) remain in CR with a median follow-up of 3 months (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24 patients) and 60% of the primary refractory disease cases (three of five patients) achieved CR. Of these 13 responders, six are alive (three continuing in CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20 months), and seven have died with a median survival of 7 months (range, 0 to 12 months). Of the 52 patients who have achieved CR, 84% did so with one course of treatment and 16% with two courses. The presence of normal cytogenetic analysis or favorable chromosomal aberrations significantly improved overall CR rates. The patients in this study had significantly more unfavorable cytogenetic abnormalities than the historic controls. Reported toxicity was hepatic in 13%, cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable efficacy of idarubicin to other anthracyclines in remission induction of acute myeloid leukemia, with a promising role in relapsed/refractory disease.

Successful allogeneic bone marrow transplantation in juvenile CML: conditioning or graft-versus-leukaemia effect?

Allogeneic BMT is the treatment of choice for juvenile CML (JCML). This has been successful following conditioning with cyclophosphamide (120 mg/kg) and total body irradiation (TBI) (10-15.75 Gy). However, busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) (Bu/Cy) conditioning has been reported to be insufficient to eradicate the malignant clone in JCML. We report successful BMT and eradication of the disease at 18 months follow-up in a child 15 months old at presentation, who was conditioned with busulphan 20 mg/kg and cyclophosphamide 200 mg/kg, with the addition of splenic irradiation. Despite using higher than conventional doses of busulphan, pharmacokinetic analysis revealed very low busulphan peak levels and rapid excretion. As a possible consequence, only partial chimerism was achieved, but full engraftment ensued following the discontinuation of cyclosporin A, rebound donor lymphocytosis and the onset of acute GVHD. We suggest that host resistance to engraftment and tumour elimination was overcome by removing a suppressive effect on donor lymphocytes, allowing a graft-versus-leukaemia effect.

Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature.

Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had AML M4Eo and, following treatment with adriamycin, cytosine arabinoside, and 6-thioguanine, all achieved complete remission (CR). Neither patient with del(16)(q22) had typical M4Eo morphology at diagnosis; CR was achieved in one and one had resistant leukaemia. Patients with other abnormalities of 16q had blasts of diverse morphology and, although morphologically abnormal eosinophils were seen in three patients, this was not as marked as in the patients with inv(16). CR was achieved in two of the four patients with other abnormalities of 16q but duration of remission was short in both cases. These results suggest that most patients with del(16)(q22) and other abnormalities of 16q22 do not have typical AML M4Eo. Such patients tend to have a worse prognosis, and are more likely to have complex karyotypes typical of secondary leukaemia.

A myelokathexis-like variant of myelodysplasia.

A 34-year-old woman presented with pancytopenia, profound neutropenia and repeated infections. A bone marrow specimen revealed hypercellularity with trilineage dysplasia and bizarre granulocytic morphology identical to that of the rarely reported myelokathexis. Investigations revealed defects in platelet and neutrophil functions and markedly reduced colony-to-cluster ratio in bone marrow culture. She required treatment with antibiotics, surgical intervention for a gangrenous abdominal wall, and eventually underwent a successful allogeneic bone marrow transplant from her sister. This case suggests that myelokathexis is an unusual form of myelodysplasia with a relatively benign course and presenting at a young age.