Diagnosis Of Acute Lymphoblastic Leukemia Research Articles

Ovarian rhabdomyosarcoma presenting as leukemia case report

A condition of pure ovarian rhabdomyosarcoma in a 16-year-old female is described. The tumor presented with a leukemia-like picture, with extensive peripheral blood and bone marrow involvement which led to an initial diagnosis of acute lymphoblastic leukemia. The diagnosis was achieved at autopsy and was supported by ultrastructural findings of Z-band-like material and alternating thin and thick filaments.

Ellie: A Child's Fight Against Leukemia

In this book, the author has described the story of a 4-year-old girl from the time of her diagnosis of acute lymphoblastic leukemia (ALL) to a period six months beyond a bone marrow transplantation done after her first relapse. The book was copyrighted in 1982, and its medical aspects are reasonably up to date and accurate. Certainly, one would not go to this book for a treatise on therapy for ALL or a discussion of the role of bone marrow transplantation in the treatment of leukemia. The medical aspects, however, are presented in such a fashion that they are accessible to a lay person, yet not so oversimplified as to lose a sense of validity in presentation. Much of the book is given over to describing the reactions and responses of the various people involved. Certainly, children and families behave in variable ways, and the author makes no attempt to

Erysipelaslike Lesions and Hyperesthesia as Manifestations of Pseudomonas aeruginosa Sepsis

PSEUDOMONAS aeruginosais an important cause of sepsis in immunocompromised patients.1Systemic infection withP aeruginosamay have a variety of dermatologic manifestations, including ecthyma gangrenosum,2deep-seated nodules,3,4abscesses, vesicles, and cellulitis.5,6We describe a leukemic patient with different cutaneous manifestations ofP aeruginosainfection. Report of a Case A 20-year-old man went to his local physician with a history of fever, malaise, and sore throat. A right peritonsillar abscess and hepatosplenomegaly were present. The abscess was incised but not cultured. Hematocrit value was 26%; WBC count, 16,200/cu mm, with 43% blast forms; and platelet count, 3,000/cu mm. Bone marrow aspiration confirmed the diagnosis of acute lymphocytic leukemia (null cell). The patient was hospitalized, and therapy with vincristine sulfate, prednisone, and asparaginase was begun. Profound neutropenia (WBC count, 200/cu mm) developed. Blood, platelet, and WBC transfusions were given, and intravenous (IV) administration of oxacillin sodium, 65

Recovery of immune function after cessation of maintenance therapy in acute lymphoblastic leukemia (ALL) of childhood.

In previously healthy children, serum immunoglobulin levels at diagnosis of acute lymphoblastic leukemia (ALL) were entirely in the normal range. After antileukemic therapy had been given for 26-27 months, serum immunoglobulin levels were low. In 32 children these parameters could be followed for periods up to 3 years after cessation of therapy, the patients remaining in unmaintained remission. At cessation of therapy serum immunoglobulin levels were at the tenth centile of the normal range or slightly below. IgG promptly returned to normal levels and then remained in the normal range. IgA levels were restored much more slowly. Most striking was the slow and incomplete return of serum IgM to normal levels. Even after a follow-up of 3 years the mean was still subnormal. This was not accompanied by clinical signs of disturbed immunity. Our study points out that in assessing the long-term immunosuppressive effects of anticancer therapy the follow-up period must be sufficiently long.

Changes in Clonal Expression During the Course of Acute Leukemia: Possible Subsets in Childhood Leukemia<xref ref-type="fn" rid="fn2">2</xref>

We studied cell surface markers and chromosomes in the leukemia cells of a boy with the initial diagnosis of acute lymphocytic leukemia during 18 months from diagnosis to demise. During this time he received induction therapy, underwent bone marrow transplantation, and relapsed. The leukemia cells expressed three membrane phenotypes during different stages of disease: T-cell at diagnosis; T-cell, B-cell, and monocyte during the induction period; T-cell in the first relapse after bone marrow transplantation; and T-cell and B-cell during the terminal stage. Some cells expressed markers of two cell types, indicating a common origin of these cells. Cytogenetic studies during post-transplantation relapse showed abnormal marker chromosomes that indicated two major sublines. However, there was enough sharing of other aberrant chromosomes to suggest that these two populations presented sublines within the same neoplastic clone. We suggest that these leukemia cells were derived from a pluripotential cell prior to differentiation into cells of the lymphoid and monocytic series. This particular case may represent a subset of acute leukemia and may account for the resistance to conventional therapy.

Second Malignancy in Acute Lymphocytic Leukemia

Sir .—I read with interest the article Second Malignancy in Acute Lymphocytic Leukemia: Review of 33 Cases by Drs Mosijczuk and Ruymann in theJournal(1981;135:313-316). In their article, they discussed the occurrence of histiocytic medullary reticulosis (HMR) after the diagnosis of acute lymphocytic leukemia (ALL). Histiocytic medullary reticulosis is a pattern of response to infection by a number of organisms. 1,2 Although originally identified by Robb-Smith as one of the causes of HMR, 3 acquired toxoplasmosis has been omitted from the list of possible causes of HMR in recent articles. In the immunocompetent host, toxoplasmosis is a benign, self-limited illness that frequently resembles infectious mononucleosis in its clinical manifestations. However, in the immunosuppressed host, toxoplasmosis occurs as an acute, fulminating illness, with prominent systemic symptoms, hepatosplenomegaly, and, occasionally, signs of CNS dysfunction. 4 If this diagnosis is not considered in an immunocompromised host, and appropriate therapy with pyrimethamine and

Childhood T‐cell acute lymphoblastic leukaemia expressing “Ia‐like” antigen: A case report

A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.

Prognostic significance of terminal transferase activity and other factors in childhood acute lymphoblastic leukemia.

Terminal deoxynucleotidyl transferase (TDT) is an intracellular biochemical marker of certain types of lymphoid precursors. Clinically, TDT serves as a useful marker of malignant lymphoblasts. TDT activity is elevated in 85–95% of cases of non-B, non-T and T-marked acute lymphoblastic leukemias, 5–10% of cases of acute myelogenous leukemia, and 30–40% of cases of chronic myelogenous in blastic phase (reviewed by Coleman and Hutton, 1981). The presence of TDT in leukemic cells is correlated with a favorable response to therapy with drugs cytocidal to lymphoblasts. There is marked variation in the activity of TDT in leukemic cells at diagnosis of acute lymphoblastic leukemia. In our experience values ranged from 0 to 694 units/108 nucleated cells in bone marrow from 118 children and from 0 to 1790 units/108 nucleated cells in peripheral blood from 51 children with acute lymphoblastic leukemia (Hutton et al, 1979). There are no studies testing the prognostic significance of these quantitative variations in level of TDT at diagnosis. Similarly, there are no studies testing whether quantitative measurements of TDT activity during remission of leukemia can predict relapse of disease.

The occurrence of leukemia in patients with the Shwachman syndrome

THE SHWACHMAN SYNDROME is a rare autosomal recessive disease associated with exocrine pancreatic insufficiency, skeletal anomalies such as metaphyseal dysostosis, growth retardation, recurrent infections, and hypoplastic hematologic abnormalities, commonly presenting as neutropenia but also with hypoplastic anemia, thrombocytopenia , or pancytopenia. 1-a Recently, several isolated cases of leukemia have been identified in patients with the Shwachman syndrome? -~ Two additional cases of leukemia associated with EPI are described. A common palhophysiologic process in these patients is suggested. CASE REPORTS Patient 1, a 20-month-old boy, presented with diffuse edema, ascites, and failure to thrive. Height and weight were less than the fifth percentile for age. Laboratory studies documented hypoalbuminemia (1.5 gm/dl) with a total protein concentration of 3.4 gm/dl, hemoglobin of 10 gm/dl, white blood count of 14,300/p,1 with normal differential (47% granulocytes), and platelet count of 538,000//d. Urinalysis and sweat chloride determinations were normal. The stools contained markedly increased fat and undigested meat fibers. Duodenal intubation revealed absent trypsin activity in the fluid obtained, and a small bowel biopsy demonstrated subtotal villus atrophy consistent with a malnourished state. The patient was given an elemental diet with resolution of the edema, and subsequently he was advanced to a normal diet with oral pancreatic enzyme and vitamin replacement. Two months later a complete blood count revealed hemoglobin of 13 gm/dl, platelet count 687,000//d, and WBC 11,800/td with an absolute neutrophll count of 2,600/#1. Acute leg pain occurred one month later, when the hemoglobin concentration was 10.4 gm/dl, platelet count 136,000//B, and WBC 33,500/,al with 5% granulocytes and 67% leukemia cells. Bone marrow aspirate and biopsy confirmed the diagnosis of acute lymphocytic leukemia, L-I morphology, with positive periodic acid Schiff staining lymphoblasts. Hematologic remission was successfully induced with vincristine, prednisone, and L-asparaginase. Central nervous system prophylaxis was administered and the patient has

Terminal transferase in acute lymphoblast leukemia in remission.

Terminal deoxynucleotidyl transferase (TdT) is a marker for the diagnosis of acute lymphoblastic leukemia. To determine its value as an indicator of bone marrow remission or impending relapse, serial remission marrows (less than 5% blasts) from 49 patients who had acute lymphoblastic leukemia were examined for TdT by immunofluorescence over the period of a year. Thirty-eight patients (78%) had less than 1% TdT-positive cells. Eleven patients (22%) had slightly elevated levels of TdT (2%-7%) at some time during the study. of these eleven, only two had relapses; however, neither patient had greater than 1% TdT-positive cells within the three months before the relapse. Therefore, it appears that the presence of slightly increased numbers of TdT-positive cells in acute lymphoblastic leukemia remission bone marrows (2%-7%) does not denote impending relapse. In addition, most of the patients with acute lymphoblastic leukemia in remission had less than 1% TdT-positive cells.

Immunologically Defined Subclasses of Acute Lymphoblastic Leukaemia in Children: their Relationship to Presentation Features and Prognosis

Summary. Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, ‘null’ (or ‘unclassified’) ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal non-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in ‘null’ ALL, and highest in cALL (P trend < 0·0001; P=0·0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or ‘null’ ALL group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic

Immunologically Defined Subclasses of Acute Lymphoblastic Leukaemia in Children: their Relationship to Presentation Features and Prognosis

Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.

Recent Approaches to the Treatment of Acute Lymphocytic Leukemia in Childhood

Acute lymphocytic leukemia (ALL) is the most common malignancy in childhood accounting for 35--40% of cancers in this age group. At the time of diagnosis approximately a trillion ( 1012) leukemic cells are present throughout the body (1). The bone marrow has been replaced and sup­ pressed by leukemic cells causing a cessation of normal blood cell produc­ tion. Previously both physicians and parents equated a diagnosis of acute lymphocytic leukemia with a certainty of rapid death. This dire prognosis has changed dramatically in the last 20 yeats. Now a complete bone marrow remission can be induced in 95% of children with ALL. Moreover, one half of these children will have a prolonged leukemia-free survival and probable cure. This chapter reviews the therapeutic advances that have led to this great improvement in survival, the current problems associated with this treat­ ment, and approaches to achieve more specific and effective therapy. Recent articles have summarized the first two topics (1-7), so we concentrate on new directions for therapy. Innovative new approaches are needed since the percentage of patients who achieve long-term leukemia·free survival has not increased appreciably in the last 10 years.

Occult testicular leukemia: testicular biopsy at three years continuous complete remission of childhood leukemia: a Southwest Oncology Group Study.

Between June 1977 and December 1978, occult testicular leukemia (OTL) was discovered at three years of continual complete remission (CCR) from the time of diagnosis of acute lymphoblastic leukemia (ALL) in 5 of 59 (8.5%) of males undergoing bilateral wedge testicular biopsy at 1 of 15 participating Southwest Oncology Group (SWOG) institutions. Forty-six of the 54 males with normal biopsies (78% of the total group of 59) have remained free of recurrent ALL at a median of 18 months (range 13 to 23 months) since the biopsy procedure, whereas eight have relapsed for the first time--five bone marrow (BM), one sclera, one simultaneous BM and testes, and one testes--at a median of 12.5 months (range 4 to 22 months) after the normal testicular biopsy. With aggressive therapy after biopsy in the five boys with OTL, one has died 19 months after biopsy (after two BM relapses), one is alive 21 months after biopsy (after two BM relapses), and three are alive and free of recurrent ALL 13, 16, and 19 months, respectively, since the diagnosis of OTL.

A score at diagnosis for predicting length of remission in childhood acute lymphoblastic leukaemia.

Thirty-two variables at diagnosis of acute lymphoblastic leukaemia (ALL) were studied in an unselected population-bases series of 209 children. Twelve variables had individually a statistically significant effect on the duration of first remission. A multivariate analysis using data on the 199 children who went into complete remission showed that all significant variation in remission times could be explained by only 3 variables acting simultaneously. These were the total white blood count (WBC) at diagnosis, the Franco-American-British (FAB) classification of blast morphology and the percentage of lymphoblasts with PAS+ coarse granules or blocks. A simple scoring system (for WBC add 1 if less than 20 X 10(9)/1, add 2 if 20 - 50 X 10(9)/1, add 3 if greater than or equal to 50 X 10(9)/1; for L2 or L3 leukaemia add 1; for PAS+ less than 5% add 1) separated patients into risk groups with widely different median lengths of first remission. Application of the risk score improves the prediction of the outcome of treatment, and the clinical trials, allows more accurate stratification, less extensive data collection and simpler analysis.

Prognostic significance of amoeboid movement configuration in lymphoid cells from children with acute lymphoblastic leukaemia.

Bone marrow smears from 72 consecutive children with a recent diagnosis of acute lymphoblastic leukaemia (ALL) have been morphologically analyzed. A high incidence of lymphoid cells with amoeboid movement configuration (AMC) seems to indicate a more favorable prognosis independently of other prognostic factors e.g. age, WBC or sex. A positive correlation between the AMC and the mitotic indices (MI) of the lymphoblasts indicates some connection between the motility and the proliferative activity of the leukaemic cell clone.

Cytological Examination of the Cerebrospinal Fluid at Diagnosis of Acute Lymphocytic Leukemia in Children

Cytological Examination of the Cerebrospinal Fluid at Diagnosis of Acute Lymphocytic Leukemia in Children

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

ADULT ACUTE LYMPHOBLASTIC LEUKAEMIA: A FIVE‐YEAR EXPERIENCE

The case histories of all patients for whom the diagnosis of acute lymphoblastic leukaemia (ALL) was made over a five-year period at the Royal Adelaide Hospital and Institute of Medical and Veterinary Science were studied. There were 34 patients with a median age of 47.5 years. Adequate follow-up was obtained on 33 patients, and their median survival was 5.4 months. The remission rate was 77% in the under-30 years age group, but only 15% in the over-30 years age group. The median duration of remission was 24 months while the median survival of remitters has not yet been reached. The median survival of non-remitters was two months with 100% being dead at 12-3 months. Of 20 patients without remission, seven died of haemorrhage and/or infection before an adequate trial of therapy had been completed, while nine patients had "adequate" intensive therapy but failed to achieve remission.

Acid Esterase in Human Lymphoid Cells and Leukaemic Blasts: a Marker for T Lymphocytes

A non-specific acid alpha-naphthyl-acetate esterase activity was investigated in human lymphoid cell populations from tonsils, blood, thymus and in different leukaemias. Four patterns have emerged. (i) The vast majority of T lymphocytes (peripheral blood, tonsils) showed a localized, intense reaction product ("T-like"). (ii) A thymocyte subpopulation expressed faint, localized enzyme activity ("Thy-like) but the majority of thymocytes showed no esterase activity. Some cells from acute lymphoblastic leukaemias with thymocyte surface characteristics had a "Thy-like" appearance. (iii) Most B lymphocytes and cells from chronic lymphocytic leukaemias were esterase negative. No activity was seen in mitogen activated peripheral blood T and B lymphoblasts from peripheral blood and in leukaemic blasts from the common form of childhood acute "lymphoblastic" leukaemia. (iv) Myeloid cells, including peripheral blood monocytes, and blast cells from acute myeloblastic and chronic granulocytic leukaemias showed an intense, diffuse reaction product (M-like). It is concluded that the modified esterase technique is a convenient marker for small mature human T lymphocytes in tissue sections and smears. It may also be helpful in the differential diagnosis of acute lymphoblastic leukaemia with T characteristics, the common form of acute "lymphoblastic" leukaemia and acute myeloblastic leukaemia.