Outcome of high-dose cytarabine-based induction therapy followed by hematopoietic stem cell transplantation in acute myeloid leukemia: influence of karyotype.

One-hundred-twenty consecutive adult patients aged 15-69 years (median 40) with acute myeloid leukemia (AML) excluding t(15;17) received induction therapy comprising idarubicin, high-dose cytarabine and etoposide. Planned post-induction treatment included two courses of moderate-intensity consolidation therapy followed by stem cell transplantation. 11 patients (9%) died during induction therapy.

Cytogenetic abnormalities additional to t(11;14) correlate with clinical features in leukaemic presentation of mantle cell lymphoma, and may influence prognosis: a study of 60 cases by FISH.

Mantle cell lymphoma (MCL), characterised by t(11;14)(q13;q32), has a poor prognosis. Many cases have additional cytogenetic abnormalities, and often have a complex karyotype. Fluorescence in situ hybridisation (FISH) was used to study 60 cases with leukaemic presentation of MCL, to determine the frequency, clinical correlations and prognostic impact of a panel of molecular cytogenetic abnormalities: 17p13 (TP53 locus), 13q14, 12 p11.

Impact of cytogenetics on the outcome of autotransplantation for acute myeloid leukemia in first remission: is the benefit of intensive pretransplant therapy limited to patients with good karyotypes?

A total of 81 adults with acute myeloid leukemia (AML) (47% favorable karyotypes) were autografted in first remission after melphalan-total body irradiation, having received 0 (n=7), 1 (n=19), 2 (n=51), or 3 (n=4) consolidation chemotherapy cycles before harvest. The cumulative 5-year incidences of relapse and transplant-related mortality were 37 and 17%, respectively. The actuarial 5-year probability of disease-free survival (DFS) was 46%.

Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients.

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade B-cell lymphoma defined in the World Health Organization classification as the leukaemic form of splenic marginal zone lymphoma. Presenting features and response to therapy have been described, but information on prognostic factors is scanty. Clinical, laboratory and follow-up data were collected on 129 patients with SLVL to determine features predicting disease behaviour and survival.

Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia.

To determine the incidence of the mixed lineage leukemia (MLL) gene rearrangements in acute myeloid leukemia (AML) without cytogenetically-detected 11q23 abnormalities, we screened 64 cases of AML at diagnosis for MLL rearrangement by FISH. Three cases (4.7%) had a MLL rearrangement detected; one was shown to have a cryptic t(11;22)(q23;q11) and another to have a t(9;11)(p21-22;q23) which had been missed by the conventional cytogenetic study.

Disease features in acute myeloid leukemia with t(8;21)(q22;q22). Influence of age, secondary karyotype abnormalities, CD19 status, and extramedullary leukemia on survival.

Over a period of 14 years, 50 patients (12 children and 38 adults) of whom 46 had acute myeloid leukemia (AML) and 4 had myelodysplastic syndrome characterized by the t(8;21)(q22;q22) translocation were referred to the Royal Marsden Hospital. The clinicopathological features of these cases were analyzed to determine the influence of age, secondary karyotype abnormalities, and expression of the lymphoid marker CD19 on event free survival, and presence of extramedullary leukemia on overall survival. They were treated with a variety of chemotherapy protocols and some had bone marrow transplantation.

Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone-based therapy for breast carcinoma.

Of 1774 patients with breast cancer given mitoxantrone (MTZ) with methotrexate (n = 492) or with methotrexate and mitomycin C (n = 1282), nine developed MDS/AML after a median of 2.5 years. Median duration of survival from diagnosis of MDS/AML was 10 months and six patients died.

The impact of karyotype on remission rates in adult patients with de novo acute myeloid leukemia receiving high-dose cytarabine-based induction chemotherapy.

One hundred and twenty-eight patients aged 15 years or over (median 34) with de novo acute myeloid leukemia (AML) received 2- or 3-drug induction chemotherapy comprising 5 days of daily high-dose cytarabine (2 g/m2 q12h) and etoposide (100 mg/m2), without (n=62, 1985-90, protocol BF11) or with (n=66, 1990-97, protocol BF12) daily 5 mg/m2 anthracycline (61 idarubicin, 5 mitoxantrone). Twelve patients with t(15;17) were not included. Evaluable karyotypes were obtained in 110 (86%): 30 (27%) favorable, 60 (55%) intermediate, and 20 (18%) adverse.

Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine.

We report the long-term follow-up results on two groups of patients with hairy cell leukaemia (HCL) treated with either pentostatin (deoxycoformycin) or cladribine (2-chlorodeoxyadenosine). 165 HCL patients received treatment with pentostatin (between 1986 and 1994), and 45 were treated with cladribine (between 1992 and 1997). Age and sex characteristics were similar in the two groups.

Monosomy X as the sole cytogenetic abnormality in acute lymphoblastic leukemia: a report of two new patients.

Monosomy X as the sole acquired cytogenetic abnormality is usually found in myeloid hematological malignancies, especially those with myelodysplastic features. Only three cases of acute lymphoblastic leukemia (ALL) with this abnormality have been previously reported. We add two cases to this series and comment on the likelihood of a tumor suppressor gene being located on the X chromosome.

The proportion of clonal divisions varies in different hematologic malignancies. The United Kingdom Cancer Cytogenetics Group (UKCCG) [corrected].

The detection of clones by conventional cytogenetic studies in diagnostic hematoncology is heavily subject to the effects of many biological and laboratory factors, one of which is the number of divisions analyzed. Data from 20 laboratories were combined to get an impression of the true frequency of clonal divisions for comparison with the theoretical models that have been previously used to set laboratory policies. This study showed that low-percentage clones were more common in the myelodysplastic syndromes and that high-percentage clones were more common in acute myeloid leukemia than in acute lymphoblastic leukemia (ALL), although the clone detection rate in ALLs is higher.

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

This paper reports clinical and cytogenetic data from 125 cases with t(9;11)(p21-22;q32) which were accepted for a European Union Concerted Action Workshop on 11q23. This chromosome abnormality is known to occur predominantly in acute myeloid leukemia (AML) FAB type M5a and less often in AML M4; in this series it was also found to occur, uncommonly, in other AML FAB types, in childhood acute lymphoblastic leukemia (ALL) (nine cases), in relatively young patients with myelodysplastic syndrome (MDS) (five cases), acute biphenotypic leukemia (two cases), and acute undifferentiated leukemia (one case). All age groups were represented but 50% of the patients were aged less than 15 years.

Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia.

We have analysed the prognostic influence of cytogenetic findings at diagnosis in a group of 502 children with acute lymphoblastic leukaemia (ALL), treated on MRC UKALL X, in whom clonal cytogenetic abnormalities were detected at diagnosis. Despite the overall improvement in outcome in children treated on this protocol compared with previous trials, some cytogenetically-defined groups were still associated with a poor outcome and ploidy retained some prognostic significance. Patients with high hyperdiploid ALL (39% of those with clonal abnormalities) had a favourable outcome with event free survival of 71% at 5 years.

Sequential development of myelodysplasia and acute myeloid leukemia but with no karyotypic evolution after autografting in a patient with Philadelphia positive acute lymphoblastic leukemia.

A woman with Philadelphia chromosome-positive c-ALL with +8 and i17q in addition underwent an unpurged blood stem cell autograft after 200mg/m2 melphalan in first relapse. Maintenance therapy with 6-mercatopurine was started following the autograft. Moderate pancytopenia developed after 4 months, and myelodysplasia (refractory anemia) was diagnosed which rapidly evolved into AML.

Bilineal acute leukemia of B and T lineage with a novel translocation t(9;17)(p11;q11).

We describe a case of bilineal leukemia in a 5-year old boy with a rare immunophenotype and the novel translocation t(9;17)(p11;q11) as the sole chromosomal abnormality. Two immunologically distinct blast cell subsets expressed T-markers (CD2, CD5, CD7) and common ALL markers (TdT, CD19, CD22, CD10), respectively. Both cell populations were CD34 negative.

Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia (APL) has been associated with a favourable prognosis in many studies of acute myeloid leukaemia. A series of 54 patients treated at the Royal Marsden Hospital between 1979 and 1996, with APL and the t(15;17) chromosome translocation at presentation, was examined for the effect of additional chromosome abnormalities in their presentation karyotype on survival. The patients were aged between 2 and 62 years with a median age of 31 years.

Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women.

Melphalan has rarely been used as a single agent for conditioning prior to allogeneic marrow transplantation. Twenty-eight patients (median age 19.5 years) undergoing allogeneic BMT for acute leukemia (n = 26) or lymphoblastic lymphoma (n = 2) in first remission (n = 10) or beyond (n = 18) from HLA-identical siblings received 240 mg/m2 melphalan.

Analysis of clonal rearrangements of the Ig heavy chain locus in acute leukemia.

Clonal rearrangements of the Ig heavy chain (IGH) locus occur in nearly all cases of B-cell precursor acute leukemia (BCP-ALL). Some of these rearrangements may be detected by polymerase chain reaction (PCR) using VH gene framework III (FRIII) and JH consensus primers. However, about 20% of BCP-ALLs fail to amplify with this technique.

Platinum agents and secondary myeloid leukaemia: two cases treated only with platinum-based drugs.

With the increasing use of chemotherapy for many different primary malignancies, secondary or therapy-related acute myeloid leukaemias (AML) and myelodysplastic syndromes (MDS) are becoming more common. The risk of developing sAML has been estimated to be between 2% and 10%, depending upon the type, duration and dosage of previous therapy (Michels et al, 1985; Shulman, 1993; Robinson & Mertens, 1993; Ballen & Antin, 1993). It is therefore one of the most serious long-term complications of current cancer treatment and is likely to increase as longer survival rates for the primary tumour are achieved.

der(16)t(1;16)(q21;q13) as a secondary change in alveolar rhabdomyosarcoma. A case report and review of the literature.

Alveolar rhabdomyosarcoma is an aggressive childhood tumor that exhibits muscle cell differentiation. Cytogenetically, it is characterized by t(2;13)(q35;q14); no consistent secondary abnormalities have been reported. Cytogenetic analysis of bone marrow in a case of alveolar rhabdomyosarcoma revealed t(2;13)(q35;q14) and der(16)t(1;16)(q21;q13).

Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Between 1986 and 1995, 19 patients with Philadelphia chromosome-positive (Ph + ) acute lymphoblastic leukemia underwent 20 autologous (n = 9) or allogeneic (n = 11) blood or marrow transplant procedures in first (n = 12) or second (n = 3) remission, or in relapse (n = 5). Four patients died due to transplant-related causes, 11 relapsed at 3-39 months, one survives with disease which did not remit after transplant, and three are alive in continuous remission at 1, 26 and 65 months. Two of the relapsing patients are alive; one autografted patient after an allograft in second remission and one allografted patient after a donor leukocyte infusion.

Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients.

We have analysed the clinical and laboratory features in 544 patients with chronic lymphocytic leukaemia (CLL) with available cytogenetics and fluorescence in-situ hybridization (FISH) analysis for trisomy 12 in half of them, to examine the correlation between chromosome abnormalities and clinical or laboratory parameters. Five chromosome groups were defined: (1) trisomy 12 (18%), detected as the sole abnormality or associated with other changes; (2) del(13)(q12-14) (7%); (3) other abnormal karyotypes (20%); (4) normal karyotype (41%); and (5) no divisions (14%). There were no differences in the age distribution between the five groups.