Acute lymphoblastic leukaemia.

In acute lymphoblastic leukaemia (ALL) the karyotype provides important prognostic information which is beginning to have an impact on treatment. The most significant structural chromosomal changes include: the poor-risk abnormalities; t(9;22)(q34;q11), giving rise to the BCR/ABL fusion and rearrangements of the MLL gene; abnormalities previously designated as poor-risk; t(1;19)(q23;p13), producing the E2A/PBX1 and rearrangements of MYC with the immunoglobulin genes; and the probable good risk translocation t(12;21)(p13;q22), which results in the ETV6/AML1 fusion. These abnormalities occur most frequently in B-lineage leukaemias, while rearrangements of the T cell receptor genes are associated with T-lineage ALL. Abnormalities of the short arm of chromosome 9, in particular homozygous deletions involving the tumour suppressor gene (TSG) p16(INK4A), are associated with a poor outcome. Numerical chromosomal abnormalities are of particular importance in relation to prognosis. High hyperdiploidy (51-65 chromosomes) is associated with a good risk, whereas the outlook for patients with near haploidy (23-29 chromosomes) is extremely poor. In view of the introduction of risk-adjusted therapy into the UK childhood ALL treatment trials, an interphase FISH screening programme has been developed to reveal chromosomal abnormalities with prognostic significance in childhood ALL. Novel techniques in molecular cytogenetics are identifying new, cryptic abnormalities in small groups of patients which may lead to further improvements in future treatment protocols.     

Acute lymphoblastic leukaemia in pregnancy

Two cases of pregnant patients with acute lymphoblastic leukaemia (ALL) are presented. ALL is rare in pregnancy. The basic principle of ALL treatment is combination chemotherapy with sequential administration of induction, consolidation and maintenance therapy, and this also holds for ALL in pregnancy. The prognosis of ALL in pregnancy is poor and termination of the pregnancy needs to be considered.     

Acute lymphoblastic leukaemia: diagnosis and classification

Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease with distinct biological and prognostic groupings. Diagnosis relies on traditional cytomorphological and immunohistochemical evaluation of the leukaemic blasts. Subsequently, cytogenetic analysis identifies clonal numeric and/or structural chromosomal abnormalities that may be present, thus confirming the subtype classification and providing important prognostic information for treatment planning. The major chromosomal abnormalities in ALL are t(9;22)(q34;q11), t(12;21)(p13;q22), t(4;11)(q21;q23), t(1;19)(q23;p13), 8q24 translocations and hyperdiploidy. Generally, hyperdiploidy, occurring most frequently in paediatric cases, is associated with a good prognosis, while hypodiploidy confers a poor prognosis. Among structural chromosomal abnormalities, the t(9;22)(q34;q11) resulting in the BCR/ABL fusion protein, and rearrangements of the MLL gene, confer a poor prognosis in both children and adults, while t(12;21)(p13;q22), resulting in the TEL/AML1 fusion protein, and del (12p) confer a good prognosis. More recently, additional diagnostic and prognostic information has been gained from fluorescence in situ hybridization (FISH) and DNA microarray techniques.     

Acute lymphoblastic leukaemia in a child with cystic fibrosis.

The association of cystic fibrosis (CF) and acute lymphoblastic leukaemia (ALL) is extremely rare. Only three cases have been reported in the literature and all of them had a fatal outcome. In this paper we describe the case of a little girl who was diagnosed with CF (mild course) when she was five months old, and who presented at the age of five years with ALL (intermediate risk). Complete Remission (CR) was rapidly obtained with standard chemotherapy for ALL.; treatment was continued for two years without major complications and with no apparent influence on the course of CF. The patient remains alive and well and in continuous CR four years after discontinuing treatment, and six years after the diagnosis of ALL.     

Acute lymphoblastic leukaemia after bone marrow transplantation for aplastic anaemia

An 11.5-year-old girl developed acute lymphoblastic leukaemia 7 months after bone marrow transplantation for severe aplastic anaemia. Before transplantation there were neither morphologic nor cytogenetic abnormalities to suggest preleukaemia. The conditioning regimen consisted only of cyclophosphamide. At the time of development of acute lymphoblastic leukaemia, chromosome analysis showed the blasts to be of host origin with clonal abnormalities including monosomy 7. Such a preleukaemic syndrome presenting as severe aplastic anaemia is a very rare event (the case reported here is the only one of 436 patients in Seattle) and cannot be reliably excluded before transplantation.     

Acute lymphoblastic leukaemia in a child with systemic lupus erythematosus

Haematological involvement of systemic lupus erythematosus (SLE) - which ranges from the well-described haemolytic anaemia to macrophage activation syndrome - has a large impact on both morbidity and mortality. On the other hand, association between haematological malignities and SLE - in terms of pathophysiology and molecular genetics - is an obscure entity which has not been clarified evidently to date. Herein, we present a six-year-old female with the diagnosis of SLE who developed acute lymphoblastic leukaemia following a period of myelodysplasia. It could possibly be coincidental; however, persistent cytopenia, prominent dysplasia on bone marrow smears and azathioprine treatment may be considered as possible triggers for the development of leukaemia in the present case.     

Acute lymphoblastic leukaemia in childhood: cell proliferation without rest

The percentage of non-cycling blast cells in children with untreated acute lymphoblastic leukaemia (ALL) was investigated by staining smears for statin, a nuclear protein specifically present in non-growing resting cells. Results were compared with purified normal CD34-positive progenitors. A low fraction of ALL and CD34-positive cells expressed statin (2.0 ± 3.8% and 2.8 ±3.1%, respectively), the growth fraction assessed by staining for the nucleolar antigen p120 was 94% in both ALL and CD34-positive cell samples. From this analysis it can be concluded that the compartment of non-replicating cells in ALL as well as in normal CD34-positive precursor cells collected from peripheral blood is very small and that most cells are cycling.     

Acute lymphoblastic leukaemia in children with Down syndrome: an updated review

Down syndrome (DS) is the most common chromosomal abnormality in children and also carries a marked increased incidence of acute leukaemia. Current therapy for acute lymphoblastic leukaemia (ALL) in children with DS offers similar treatment outcome as compared to children without DS. However, in general, there is increased morbidity associated with chemotherapy in children with DS. In recent years, a better understanding of the biology of ALL has led to the elucidation of differences in DS ALL vs non-DS ALL. Further research in these differences may provide a more targeted therapy for DS ALL, with the hopes of continuing good therapeutic outcome while decreasing the toxicities seen in these patients. This review provides an update on the current treatment outcomes and the biological differences seen in DS ALL.     

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

Summary. 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.     

Adult acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) in adults is a relatively rare neoplasm with a curability rate around 30% at 5 years. This consideration makes it imperative to dissect further the biological mechanisms of disease, in order to selectively implement an hitherto unsatisfactory success rate. The recognition of discrete ALL subtypes (some of which deserve specific therapeutic approaches, like T-lineage ALL (T-ALL) and mature B-lineage ALL (B-ALL)) is possible through an accurate combination of cytomorphology, immunophenotytpe and cytogenetic assays and has been a major result of clinical research studies conducted over the past 20 years. Two–three major prognostic groups are now easily identifiable, with a survival probability ranging from <10 to 20% (Philadelphia-positive ALL) to about 50–60% (low-risk T-ALL and selected patients with B-lineage ALL). These issues are extensively reviewed and form the basis of current knowledge. The second major point relates to the emerging importance of studies that reveal a dysregulated gene activity and its clinical counterpart. It is now clear that prognostication is a complex matter ranging from patient-related issues to cytogenetics to molecular biology, including the evaluation of minimal residual disease (MRD) and possibly gene array tests. On these bases, the role of a correct, highly personalised therapeutic choice will soon become fundamental. Therapeutic progress may be obtainable through a careful integration of chemotherapy, stem cell transplantation, and the new targeted treatments with highly specific metabolic inhibitors and humanised monoclonal antibodies.     

Acute lymphoblastic leukaemia in adults: Immunological subtypes and clinical features at presentation

Summary In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SIHON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed.The following persons participated in the immunophenotyping studies:E. van der Schoot, Central Laboratory Red Cross Blood Transfusion Service, Amsterdam;A. E. G. Kr. von dem Borne, Acad. Medical Center, Amsterdam; J.J.M. Hoffmann, Catharina Hospital, Eindhoven; P. Wijermans, Leyenburgh Hospital, The Hague; J. Mulder, Regional Immunologic Lab., Leeuwarden; J. C. Kluin-Nelemans, University Hospital, Leiden; D. J. van Rheenen, University Hospital Annadal, Maastricht; H. J. Adriaansen, Erasmus Univ., Rotterdam; M. B. van't Veer, Dr. Daniel den Hoed Cancer Center, Rotterdam; H. Lokhorst, University Hospital, Utrecht; The Netherlands.