Acute Myeloid Leukaemia with Monosomy-7 Follows Acute Lymphoblastic Leukaemia

A case report of an 8-year-old girl who developed acute myeloid leukaemia (AML) following the successful treatment of acute lymphoblastic leukaemia (ALL) is presented. Haematological and cytochemical evidence for the two types of leukaemia is given. This is reinforced by the cytogenetic findings. After 2 years' treatment for ALL the patient became pancytopenic and marrow depression continued even when all treatment was stopped. Marrow cells monosomic for chromosome-7 (45 XX -7) were first seen 2 months before the onset of progressive pancytopenia when blood parameters were normal. Both during the pre-leukaemic and frankly leukaemic stages of the myeloid neoplasm, cells with monosomy-7 constituted the dominant cell line in the marrow. This suggests that in this case the preceding pancytopenia was part of the malignant change and that the chromosomal change was one of the earliest events in the neoplastic process. Other reports of AML following cytotoxic therapy for treatment of malignant diseases as well as for non-malignant conditions are briefly reviewed and the neoplastic mechanisms under these conditions are discussed. There is some evidence that in the case reported here genetic factors may have been at least as important as environmental conditions in triggering off the second malignant change.     

Cytochemistry and Membrane Markers in Acute Lymphatic Leukaemia (ALL)

136 patients suffering from ALL were subdivided into 5 subtypes (C-ALL, C/T-ALL, pre-T-ALL, B-ALL) according to rosetting tests and using specific antisera directed against membrane antigens. In addition, leukaemic blasts of all patients were investigated according to morphological and cytochemical criteria. In APh and ANAE, indices and the percentages of cases showing a granular staining pattern were high in pre-T- and in T-ALL, but low in C/T- and in C-ALL. PAS-staining, conversely, was more pronounced in C/T- and C-ALL. APh proved to be more discriminative for recognition of the T- and pre-T-ALL subgroups than ANAE, but ANAE-cytochemistry may be useful to detect contaminating normal T-lymphocytes in ALL. Receptors for C₃ were more frequent in C- and in T-ALL than in C/T- and in pre-T-ALL, receptors for F_c were distributed equally among all subtypes. Positivity of C₃- and F_c-receptors was not correlated with cytochemical results. Morphological criteria were not sufficient for subclassification of ALL; the combination of APh- and PAS-staining, however, is valuable to differentiate between C-subgroups and T-subgroups.     

Long-term Abnormalities in T and B Lymphocyte Function in Children following Treatment for Acute Lymphoblastic Leukaemia

S ummary . T and B lymphocyte function as assessed by pokeweed mitogen stimulation and concanavalin A suppression was studied in 40 children with acute lymphoblastic leukaemia who were in remission and off all treatment. Both plasma cell and immunoglobulin production was reduced in off-treatment patients, particularly in those who had received cyclophosphamide as part of their treatment. The ability to suppress immunoglobulin production was also significantly reduced in these patients. These abnormalities were long-standing and were apparent up to 5 years after stopping treatment with no indication of a return to normality. No clinical correlations have been observed.     

Subclassification in Acute Lymphoblastic Leukaemia: Acid Phosphatase Reaction and Immunological Markers in Relation to Clinical Features

A prospective, comparative study of cytochemical and immunological markers and clinical features was undertaken in 44 patients with ALL (children and adults). 12 patients (27%) had T-ALL, 1 patient (2%) B-ALL and 31 patients (71%) (non-T, non-B)-ALL. E-rosetting lymphoblasts ranged from 35 to 96% (median: 61), highest when AET-treated SRBC were used as indicator cells. All 12 E-rosette positive cases were strongly acid phosphatase (AcP)-positive, showing a homogeneous pattern of distinct granular AcP-activity in more than 85 % of the lymphoblasts (median: 96 %) significantly different from the median of 26 % granulated blasts found in the (non-T, non-B)-ALL cases. Counting blasts with granular AcP-activity proved to be both easier than using a scoring system for the AcP-reaction and more efficient in terms of discriminating ability between the subgroups. Significant clinical and haematological features characterizing the T- and AcP-positive cases included: (1) Predominance of young adult men, (2) presence of a mediastinal mass, (3) involvement of skin and serous membranes, (4) only slightly affected haemoglobin concentration at presentation, (5) difficulty in obtaining complete remission, (6) shorter duration of first complete remission and (7) shorter survival rate. It is confirmed that AcP-staining of lymphoblasts is an easy, reproducible and inexpensive method for identifying the T-cell variety of ALL.     

Chromosome Studies in Acute Lymphoblastic Leukaemia (ALL)

Chromosome banding studies of the bone marrow were performed in 35 adult (> 14 years) patients with acute lymphoblastic leukaemia (ALL). Surface marker analysis was done in 24 of these and revealed 4 B-ALL, 5 T-ALL and 15 non-T non-B ALL. Most patients were studied at diagnosis before any treatment. A clonal karyotypic abnormality was found in 16 patients (46 %) initially. A Philadelphia chromosome was found in 3 patients, all belonging to the non-T non-B group. 5 patients, who all had blast cells with morphologic characteristics of Burkitt type L₃, were found to have bone marrow cells with a 14q+ marker chromosome. In at least 4 cases this was due to a t(8;14). The cytogenetic findings showed some correlation to the ALL subgroup, but not to the response to treatment or the prognosis.     

Treatment of Acute Lymphoblastic Leukaemia in Adolescents and Adults

From Jan, 1970, to Dec, 1978, 86 previously untreated adolescents and adults with acute lymphoblastic leukaemia were treated in the University Hospitals at Leiden and Nijmegen. Remissions were induced with vincristine and prednisone. If necessary an anthracyclin derivate was added. 73 Patients (85%) achieved a complete remission. CNS leukaemia prophylaxis was given to 64 patients. Two different schedules were used. 35 patients received cranial irradiation with concomitantly intrathecal injections of methotrexate (I+M) after remission had been achieved, and 29 intrathecal methotrexate (M) alone given peridiocally during the remission induction and maintenance treatment. No CNS leukaemia prophylaxis was given to 9 patients (O). Relapses were confined to the CNS alone in 5 cases (group I+M: 1 case; group M: 1 case; group O: 3 cases), to the bone marrow in 40 cases, and to the bone marrow and CNS concurrently in 5 cases (group I+M: 4 cases; group M: no cases; group O: 1 case). A second remission was obtained in 28 patients (56%). The majority of these patients did not receive further CNS prophylaxis. A second relapse of the leukaemia was seen in the majority (23 patients). CNS involvement was found in 6 of these 23 patients. Prophylactic treatment of the CNS in adult acute lymphoblastic leukaemia is mandatory. In our group of patients both schedules of prophylaxis appeared equally effective in preventing CNS leukaemia.     

Morphological Criteria for Prognostication of Acute Lymphoblastic Leukaemia

S ummary . Thirty-nine children with acute lymphoblastic leukaemia were divided into three groups according to proportion of macrolymphoblasts (MLb) (> 12 μm) in the pretreatment bone marrow: Group 1: 10 patients with MLb less than 10%; Group 11: 17 patients with 11–25% MLb; Group 111: 12 patients with MLb over 26%. The miorphologic findings were correlated with the clinical data, and it was noted that none of Group I patients had relapses for a median period of observation of 57 mth. In Group 11, 14 of 16 patients (one patient was lost to follow-up for first remission duration) had relapses, with a median first remission duration of 15 mth. In Group 111, 11 of 12 patients had relapses with a median first remission duration of 12 mth. Our data indicate that the microlymphoblastic variety of ALL has a better prognosis ( P < 0.01) when the proportion of MLb in the pretreatment bone marrow is 10% or less.     

HLA-Cw4 Association with Acute Lymphoblastic Leukaemia in Sicilian Patients

The HLA frequencies of 50 Sicilian patients affected with acute lymphoblastic leukaemia (ALL) were examined. The frequency of Cw4 antigen was significantly increased in patients. Thus results obtained in our homogeneous population confirm in part previous reports suggesting that Cw4-related genetic factors might be involved in the susceptibility to aetiological or pathogenetic mechanisms which play a role in some haematological malignancies.     

Fc and C3 Receptors as Membrane Differentiation Markers of Acute Myelogenous Leukaemia Cells

Acute myelogenous leukaemia cells (AML) and cells of chronic myelogenous leukaemia blast crisis (CGL-CB) were examined for the presence of receptors for Fc IgG fragment (FcR), receptors for the complement components (CR1 and CR2), and the surface immunoglobulins including the light kappa and lambda type chains. The leukaemia blasts were found to be the cells poor in receptors and poorly differentiated. As a rule, they contained very small amount of detectable FcR, CR2, and CR1. Analysis of AML cell populations separated on the discontinuous density gradient revealed that the appearance of FcR was followed by CR2 and CR1. The CGL-CB cells were more differentiated immunologically since, in comparison with the AML cells, in greater percentage they expressed the FcR, and the receptors for complement. Assays for surface immunoglobulins indicated that they were not an active product of the leukaemic blasts, but rather exogenous in origin.     

Lymphoid Cell Surface Markers in Acute Lymphocytic Leukaemia

Peripheral blood lymphoid cells of 29 patients with acute lymphocytic leukaemia (ALL) at onset were studied for characterization of B and T membrane markers and phytohaemagglutinin responsiveness. 24 cases (83%) were classified as ‘null’ cell ALL and 5 (17%) as T-cell ALL. No relationship could be found between cytological presentation and immunological classification. Moreover, no correlation has been demonstrated between clinical-immunological parameters and prognosis, indicating that in our series of patients, assessment of cell size and surface markers were not a reliable predictor of prognosis.     

Lack of Prognostic Value of Lymphoblast Size in Acute Lymphoblastic Leukaemia

There are conflicting reports about the relationship of cell size and type to prognosis in acute lymphoblastic leukaemia (ALL). For this reason, bone marrows at diagnosis and first relapse were studied in 56 children with ALL treated on the same protocol. Lymphoblasts greater than 12 mmu in diameter were called macrolymphoblasts (MLB). Forty-one of 56 initial bone marrows had less than 20% MLB(group A), and 15 had greater than 20% MLB (group B). Median survival, complete remission rate, first remission duration, and the distribution of CNS leukaemia were similar in both groups. First relapse marrows were examined from 50 patients and a significant increase in MLB compared to initial pre-treatment bone marrows (18% vs 8%) was found.     

Lack of Correlation of Lymphoblast Cell Size with Presence of T-Cell Markers or with Outcome in Childhood Acute Lymphoblastic Leukaemia

The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 μm, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T- and B-cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)—a T-cell marker. E-rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T-cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.     

The HL-A System in Lymphoblastic Leukaemia

S ummary The HL-A system was studied in 58 Caucasian patients with acute lymphoblastic leukaemia and their available close relatives. No gross disturbance in the distribution of the internationally defined antigens was found in the patients or their families. The high frequency of the FJH antigen is discussed. Segregation ratios within the families were, as expected, on a random basis. The haplotypes occurring most frequently in the patients were those found also to be commonest in the normal population. Suceptibility to aute lymphoblastic leukaemia could thus not be related to any particular HL-A phenotype or genotype.     

DNA Synthesis in Thymic-Acute Lymphoblastic Leukaemia

Deoxyribonucleoside triphosphate (dNTP) concentrations were measured in bone marrow and peripheral blood leucocytes from seven patients with acute Thy-lymphoblastic leukaemia (Thy-ALL), 12 patients with acute myeloblastic leukaemia and 15 patients with acute non-T, non-B lymphoblastic leukaemia (c-ALL), and in thymocytes from patients with myasthenia gravis. Labelled thymidine and deoxycytidine incorporation into DNA was also studied.
In Thy-ALL, dNTP concentrations were markedly increased compared with those in the other acute leukaemias. The dNTP concentrations in thymocytes were, however, similar to those in Thy-ALL. ³H-nucleoside incorporation studies showed a marked difference in labelled deoxycytidine incorporation and particularly in the deoxycytidine/thymidine DNA labelling ratio between Thy-ALL and the other cell types.
We conclude that the pathways of DNA synthesis in Thy-ALL blasts are different from those in the cells from other acute leukaemias and some but not all these differences may correspond to differences between normal cortical thymocytes and bone marrow cells.     

Immunological and Chromosomal Studies in First-Degree Relatives of Children with Acute Lymphoblastic Leukaemia

. Immunoglobulins (IgG, IgM and IgA) were estimated in sera from mothers and siblings of children with acute lymphoblastic leukaemia (ALL) and in sera from appropriate controls. The distribution of IgA titres was significantly lower in the siblings of leukaemic children than in control children and that of IgM was significantly higher in mothers of leukaemic children than in control mothers.     

Acute Lymphoblastic Leukaemia with Microfilaria: A Rare Coincidence in Bone Marrow Aspirate

Microfilariae in bone marrow aspirates have been reported occasionally, but until now no case has been reported in association with acute leukaemia. This is a unique finding, not mentioned in literature. Microfilariae are seen mainly in peripheral blood smears (PBS) and rarely in bone marrow aspirate, but this surprisingly did not show any parasite in PBS. Meticulous examination of bone marrow smears revealed acute lymphoblastic leukaemia and a few interspersed microfilariae. This rare combination, reported for the first time, definitely needs a space in literature.     

HLA Haplotypes and Long Survival in Childhood Acute Lymphoblastic Leukaemia Treated with Transfer Factor

Association between HLA haplotypes and a long survival was investigated in 116 children with acute lymphoblastic leukaemia. It was found that patients with A2 B12 and/or A2 B40 haplotypes survived longer than patients without these two haplotypes. Since all children were treated with transfer factor obtained from their relatives, it is suggested that children possessing A2 B12 or A2 B40 haplotypes may respond better to this type of immunotherapy.     

Adenosine Deaminase Activity in Acute Lymphoblastic Leukaemia: Cytochemical,Immunological and Clinical Correlations

Adenosine deaminase (ADA) activity has been assessed in lymphoid cells of 23 patients with acute lymphoblastic leukaemia (ALL) in order to attempt a further characterization of ALL cells in addition to the well known cytochemical and immunological T and B lymphoid cell markers. ADA activity did not show any correlation with the immunological characterization of the patients investigated; in fact a wide range of ADA activity was observed with levels ranging from 0 to 32 U in T-ALL patients and nearly similar values (from 1.8 to 36 U) in the group of non T — non B ALL cases. Normal values ranged from 2 to 5 U (mean 2.9 U; s.d. ± 0.8). Some cytochemical patterns (acid phosphatase and PAS) appeared well correlated with T markers of lymphoid cells, whereas they showed no significant relationship with ADA activity.     

Myelodysplastic syndrome transformed into Acute Lymphoblastic Leukaemia (FAB:L3)

Myelodysplastic syndrome (MDS) is recognized as a preleukaemic disorder with a variable risk of transformation to acute myeloid leukaemia. Usually the blast cells in leukaemia are transformed after MDS displays a myeloid phenotype. Even though lymphoid progression had been reported previously, most displayed myeloid-lymphoid hybrid or early B phenotype. We report a case of an elderly man who had MDS transformed into Acute Lymphoblastic Leukaemia (ALL:L3) which is a rare lymphoid transformation.     

Cell Membrane Receptors in a Case of Human Acute Monocytic Leukaemia

A study of membrane receptors on peripheral blood mononuclear cells from a patient with acute monocytic leukaemia is presented. Fc and (C) receptors which are found on normal monocytes were strongly expressed on the leukaemic cells. Electron microscopy and the cultural characteristics of these cells are also described.