scholarly journals Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 69-75 ◽  
Author(s):  
SC Raimondi ◽  
DL Williams ◽  
T Callihan ◽  
S Peiper ◽  
GK Rivera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Manifestations ◽  
Chromosome 12 ◽  
Cell Phenotype ◽  
Reciprocal Translocations ◽  
Hla Dr ◽  
Modal Chromosome Number ◽  
Failed Induction ◽  
Morphologic Type

We studied the presenting clinical and biologic features of 23 children with acute lymphoblastic leukemia (ALL) whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12. Nineteen of the abnormalities were assigned to the 12p12 breakpoint. The median age of the children was 5 years (range 2 to 13 years) and their initial leukocyte counts ranged from 1,800 to 424,000/microL (median 30,000/microL). Twenty-one patients (91%) had common phenotype ALL (CALLA+, HLA-DR+), including three cases with a pre-B cell phenotype (CIg+). The remaining two cases were T cell in origin. The French-American-British (FAB) morphologic type of lymphoblastic leukemia was L1 in all cases but one. With a median follow-up of 11 months, four patients have relapsed and another failed induction therapy. The modal chromosome number in all cases was less than 50. Three distinct cytogenetic patterns, with apparently similar clinical manifestations, were noted: terminal deletions of chromosome 12 in 10 cases, apparently balanced reciprocal translocations in 6, and unbalanced translocations in 7. All translocations were between the 12p arm and different donor chromosomes except for chromosomes 7, 9, and 17, which participated twice. Only two patients had identical translocations: t(7;12)(q11;p12). This unusual variation in donor chromosomes and breakpoints suggests that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12. The relatively high frequency of the 12p abnormalities in this study (10% of all completely banded cases seen over a 35-month period) warrants further investigation.

scholarly journals Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 69-75 ◽  
Author(s):  
SC Raimondi ◽  
DL Williams ◽  
T Callihan ◽  
S Peiper ◽  
GK Rivera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Manifestations ◽  
Chromosome 12 ◽  
Cell Phenotype ◽  
Reciprocal Translocations ◽  
Hla Dr ◽  
Modal Chromosome Number ◽  
Failed Induction ◽  
Morphologic Type

Abstract We studied the presenting clinical and biologic features of 23 children with acute lymphoblastic leukemia (ALL) whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12. Nineteen of the abnormalities were assigned to the 12p12 breakpoint. The median age of the children was 5 years (range 2 to 13 years) and their initial leukocyte counts ranged from 1,800 to 424,000/microL (median 30,000/microL). Twenty-one patients (91%) had common phenotype ALL (CALLA+, HLA-DR+), including three cases with a pre-B cell phenotype (CIg+). The remaining two cases were T cell in origin. The French-American-British (FAB) morphologic type of lymphoblastic leukemia was L1 in all cases but one. With a median follow-up of 11 months, four patients have relapsed and another failed induction therapy. The modal chromosome number in all cases was less than 50. Three distinct cytogenetic patterns, with apparently similar clinical manifestations, were noted: terminal deletions of chromosome 12 in 10 cases, apparently balanced reciprocal translocations in 6, and unbalanced translocations in 7. All translocations were between the 12p arm and different donor chromosomes except for chromosomes 7, 9, and 17, which participated twice. Only two patients had identical translocations: t(7;12)(q11;p12). This unusual variation in donor chromosomes and breakpoints suggests that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12. The relatively high frequency of the 12p abnormalities in this study (10% of all completely banded cases seen over a 35-month period) warrants further investigation.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

scholarly journals Evidence for clonal development of childhood acute lymphoblastic leukemia

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 902-907
Author(s):  
LW Dow ◽  
P Martin ◽  
J Moohr ◽  
M Greenberg ◽  
LG Macdougall ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Progenitor Cells ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Childhood All ◽  
Hla Dr ◽  
Blast Cells ◽  
Leukemic Clone ◽  
Clonal Development ◽  
Glucose 6 Phosphate Dehydrogenase

To determine whether acute lymphoblastic leukemia (ALL) is a clonal disease and to define the pattern of differentiation shown by the involved progenitor cells, we studied the glucose-6-phosphate dehydrogenase (G6PD) types in the cells of 19 girls heterozygous for this X chromosome-linked enzyme. Lymphoblast immunophenotypes were those of HLA-DR+, CALLA+ ALL (six patients); HLA-DR+, CALLA- ALL (four patients); pre-B cell ALL (two patients); T cell ALL (four patients); and undefined ALL (three patients). Malignant blast cells at diagnosis from ten patients displayed a single G6PD type, indicative of clonal disease. In contrast, both A and B G6PD in ratios similar to those found in skin were observed in morphologically normal blood cells from the same patients. The leukemic cells of three patients were examined at both diagnosis and relapse; in each instance the same G6PD type was found, consistent with regrowth of the original leukemic clone at relapse. Results of studies of cells from nine additional patients tested only at relapse were similar. Our results indicate that childhood ALL is a clonally derived disease involving progenitor cells with differentiation expression detected only in the lymphoid lineage.

scholarly journals Pre-B cell acute lymphoblastic leukemia in the newborn

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1064-1066
Author(s):  
CM Spier ◽  
CR Kjeldsberg ◽  
R O'Brien ◽  
J Marty
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Cell Marker ◽  
Ultrastructural Studies ◽  
Congenital Leukemia ◽  
Laboratory Techniques ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Marker Studies

Leukemia in the newborn is an infrequent disease that has not been well defined using modern laboratory techniques. We describe two infants, one at birth and one at four weeks, with acute lymphoblastic leukemia. The blasts from each patient were studied in great detail, using a battery of cytochemical and immunologic procedures in addition to ultrastructural studies. Immunologic cell marker studies, not previously reported in congenital leukemia, showed the lymphoblasts from each infant to be of the pre-B cell phenotype. Each infant relapsed, one after a 17-week clinical remission and the other after a 44-week remission. The former has died while the latter is in a second remission. The subtype of pre-B cell acute lymphoblastic leukemia (ALL) which in childhood appears to confer an unfavorable prognosis, may have the same significance in neonatal ALL.

Childhood Acute Lymphoblastic Leukemia With the MLL-ENL Fusion and t(11;19)(q23;p13.3) Translocation

1999 ◽  
Vol 17 (1) ◽  
pp. 191-191 ◽  
Author(s):  
Jeffrey E. Rubnitz ◽  
Bruce M. Camitta ◽  
Hazem Mahmoud ◽  
Susana C. Raimondi ◽  
Andrew J. Carroll ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Fusion Transcript ◽  
Cell Phenotype ◽  
Molecular Characteristics ◽  
Older Children ◽  
Hematopoietic Stem ◽  
Mll Gene

PURPOSE: To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23;p13.3) translocation. PATIENTS AND METHODS: A retrospective analysis of leukemic cell karyotypes obtained from patients with new diagnoses of ALL who were treated at St. Jude Children's Research Hospital or by the Pediatric Oncology Group was performed to identify cases with the t(11;19)(q23;p13.3) translocation. Molecular analyses were performed on these cases to determine the status of the MLL gene and the presence of the MLL-ENL fusion transcript. RESULTS: Among 3,578 patients with ALL and successful cytogenetic analysis, we identified 35 patients with the t(11;19)(q23;p13.3) translocation: 13 infants and 11 older children had B-precursor leukemia, whereas 11 patients had a T-cell phenotype. Although all of the cases examined had MLL rearrangements and MLL-ENL fusion transcripts, outcome varied according to age and immunophenotype. Among B-precursor cases, only two of the 13 infants remain in complete remission, compared with six of the 11 older children. Most strikingly, no relapses have occurred among B-precursor patients 1 to 9 years of age or among T-cell patients. CONCLUSION: Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis. Our results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.

scholarly journals Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4161-4166 ◽  
Author(s):  
Ursula R. Kees ◽  
Paul R. Burton ◽  
Changlong Lü ◽  
David L. Baker
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Lymphoblastic Leukemia ◽  
Homozygous Deletion ◽  
Cell Phenotype ◽  
P16 Gene ◽  
Childhood All ◽  
Risk Of Death ◽  
Increased Risk

Abstract The p16 gene (MTS1, CDKN2, p16INK4A, CDKI) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4) has been found to be deleted in various types of tumors, including leukemia, and is thought to code for a tumor suppressor gene. Our preliminary findings on eight pediatric patients with acute lymphoblastic leukemia (ALL) suggested that the survival of patients carrying a homozygous p16 gene deletion was significantly inferior to that of those without a deletion. The present study on 48 patients tested the hypothesis that the clinical outcome for pediatric ALL patients is correlated with the presence or absence of the p16 gene. Overall, nine of 48 children (18.3%) carried a homozygous p16 deletion. Such deletions were significantly more common (P = .003) among T-ALL patients (five of eight, 62.5%) than among precursor-B-ALL patients (four of 40, 10.0%). Of nine patients exhibiting p16 deletions, eight (88.9%) were classified as high-risk patients by the recognized prognostic factors of age, white blood cell count, and T-cell phenotype. The 4-year event-free survival in the study population as a whole was 72.7%. Without adjustment for other risk factors (univariate model), the presence of a homozygous p16 deletion was associated with a markedly increased probability of both relapse (P = .0003) and death (P = .002). These findings raise the question of whether the p16 deletion itself confers an increased risk of relapse after adjusting for the known risk factors. In this analysis, the estimated risk multiplier factor for relapse in patients carrying the p16 deletion was 14.0 (P = .0004) and for the risk of death 15.6 (P = .0008). We therefore conclude that the presence of a homozygous p16 deletion may well be an important risk factor for both relapse and death in childhood ALL, and that its prognostic effect is not a consequence of confounding by other factors already known to influence outcome in this disease.

scholarly journals Pre-B cell acute lymphoblastic leukemia in the newborn

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1064-1066 ◽  
Author(s):  
CM Spier ◽  
CR Kjeldsberg ◽  
R O'Brien ◽  
J Marty
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Cell Marker ◽  
Ultrastructural Studies ◽  
Congenital Leukemia ◽  
Laboratory Techniques ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Marker Studies

Abstract Leukemia in the newborn is an infrequent disease that has not been well defined using modern laboratory techniques. We describe two infants, one at birth and one at four weeks, with acute lymphoblastic leukemia. The blasts from each patient were studied in great detail, using a battery of cytochemical and immunologic procedures in addition to ultrastructural studies. Immunologic cell marker studies, not previously reported in congenital leukemia, showed the lymphoblasts from each infant to be of the pre-B cell phenotype. Each infant relapsed, one after a 17-week clinical remission and the other after a 44-week remission. The former has died while the latter is in a second remission. The subtype of pre-B cell acute lymphoblastic leukemia (ALL) which in childhood appears to confer an unfavorable prognosis, may have the same significance in neonatal ALL.

scholarly journals Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 66-70
Author(s):  
T Mohanakumar ◽  
TW Coffey ◽  
MP Vaughn ◽  
EC Russell ◽  
D Conrad
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Membrane Component ◽  
Childhood All ◽  
Antigen Present ◽  
The Common ◽  
Blood Elements ◽  
Human Primate

Abstract A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.

scholarly journals Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1112-1115 ◽  
Author(s):  
James B. Nachman ◽  
Nyla A. Heerema ◽  
Harland Sather ◽  
Bruce Camitta ◽  
Erik Forestier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Study Groups ◽  
Event Free Survival ◽  
Prognostic Implication ◽  
Monosomy 7 ◽  
Free Survival ◽  
Modal Chromosome Number

Abstract One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.

Prevalence and Patterns of Cytomegalovirus (CMV) Reactivation In Adult Acute Lymphoblastic Leukemia Patients on Chemotherapy: Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2583-2583
Author(s):  
Seema Gulia ◽  
Manju Sengar ◽  
Uma Dangi ◽  
Hari Menon ◽  
Sanjay Biswas ◽  
...  
Keyword(s):  
Viral Load ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Manifestations ◽  
High Dose ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Laboratory Parameters ◽  
Cmv Reactivation

Abstract Abstract 2583 Background: Management of acute lymphoblastic leukemia (ALL) requires use of immunosuppressive agents like high-dose steroids and antimetabolites for prolonged periods which can predispose these patients for CMV reactivation and disease. As opposed to hematopoietic stem cell transplant there has been a real paucity of literature regarding clinical manifestations and management of CMV reactivation in ALL. In countries like India with a background of high CMV seropositivity (>90%), reactivation is a serious concern in ALL patients while receiving chemotherapy. Timely recognition and treatment can avoid the morbidity and mortality as well as help maintaining dose intensity which is the key to achieve cure in ALL patients. Methods: This retrospective case series included adult ALL patients (>14 years) who were being treated with chemotherapy between July 2009 to July 2011 at a tertiary care centre and detected to have CMV viraemia (Real time quantitative PCR with Roche CMV DNA QuantKit). PCR was done in patients with possibility of CMV infection based on clinical suspicion. Case records were analyzed for demography, chemotherapy details, clinical features, laboratory parameters, viral load, antiviral therapy and response. Results: Among 203 adult ALL patients, 23 (males-18, females-5) were detected to have CMV viremia. Median age was 23 years (range, 16–44 years). Occurrence of CMV reactivation was most common during later part of induction or re-induction phase of therapy which includes high dose of steroids (14/23) followed by maintenance therapy with 6-mercaptopurine and methotrexate (5/23) and high dose cytarabine based treatment (4/23). Presenting features were: fever (19/23), fever alone (2/23) respiratory symptoms (9/23), anorexia (10/23), loose stools (8/23), abdominal pain (7/23) and splenomegaly (1/23). Abnormal laboratory parameters were: leukopenia or thrombocytopenia (14/23), deranged liver function tests (12/23). CT thorax was abnormal in 3 patients. Bacterial and fungal co-infection was seen in 5/23 patients. Median CMV viral load was 3.0 ×103 copy numbers (range, 708–1.38×106). Eighteen of these patients were treated with intravenous gancyclovir for a period of 14 days. In remaining 5 patients abnormal clinical and lab parameters improved either with antibiotic therapy or spontaneously. Median time to fever defervescence was 4 days (range, 2–5 days). Blood counts recovered after median period of 5 days (range 3–9 days). Gancyclovir related neutropenia and transaminitis developed in 1 patient. CMV titre became undetectable after a period of 2–4 weeks. Conclusion: Awareness of diverse clinical manifestations of CMV infection and high index of suspicion is important for timely diagnosis. Early diagnosis and treatment with gancyclovir reduces the morbidity, empirical use of other antimicrobials and avoids delays in administration of chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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