scholarly journals Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1784-1789 ◽  
Author(s):  
HM Kantarjian ◽  
RS Walters ◽  
TL Smith ◽  
MJ Keating ◽  
B Barlogie ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Lactic Dehydrogenase ◽  
Lymphocytic Leukemia ◽  
Risk Category ◽  
Cns Penetration

Abstract The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.

scholarly journals Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1784-1789 ◽  
Author(s):  
HM Kantarjian ◽  
RS Walters ◽  
TL Smith ◽  
MJ Keating ◽  
B Barlogie ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Lactic Dehydrogenase ◽  
Lymphocytic Leukemia ◽  
Risk Category ◽  
Cns Penetration

The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.

scholarly journals Efficacy of high-dose methotrexate in childhood acute lymphocytic leukemia: analysis by contemporary risk classifications

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 866-869 ◽  
Author(s):  
M Abromowitch ◽  
J Ochs ◽  
CH Pui ◽  
D Fairclough ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Average Risk ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Table Analysis

Abstract High-dose methotrexate (HDMTX) added to a basic regimen of chemotherapy proved superior to cranial irradiation and sequentially administered drug pairs (RTSC) in prolonging complete remissions in children with “standard-risk” acute lymphocytic leukemia. To extend this result to more contemporary risk groups, we reclassified the patients according to methods of the Pediatric Oncology Group (POG), the Childrens Cancer Study Group (CCG), the Rome workshop, and St Jude Total Therapy Study XI. By life table analysis, 70% to 78% of patients with a favorable prognosis would remain in continuous complete remission (CCR) at 4 years if treated with HDMTX. Uniformly lower CCR rates could be expected with RTSC, especially in St Jude better-risk patients. HDMTX also would show greater efficacy than RTSC in the CCG average-risk and POG poor-risk groups, but the results appear inferior to those being achieved with intensified regimens for high-risk leukemia. Although both therapies would provide adequate CNS prophylaxis in favorable-risk groups, RTSC would offer greater protection in patients classified as being in a worse-risk group by St Jude criteria. We conclude that HDMTX- based therapy, as described in this report, would be most effective in patients with a presenting leukocyte count of less than 25 x 10(9)/L, of the white race, aged 2 to 10 years, and having leukemic cell hyperdiploidy without translocations.

scholarly journals Efficacy of high-dose methotrexate in childhood acute lymphocytic leukemia: analysis by contemporary risk classifications

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 866-869
Author(s):  
M Abromowitch ◽  
J Ochs ◽  
CH Pui ◽  
D Fairclough ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Average Risk ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Table Analysis

High-dose methotrexate (HDMTX) added to a basic regimen of chemotherapy proved superior to cranial irradiation and sequentially administered drug pairs (RTSC) in prolonging complete remissions in children with “standard-risk” acute lymphocytic leukemia. To extend this result to more contemporary risk groups, we reclassified the patients according to methods of the Pediatric Oncology Group (POG), the Childrens Cancer Study Group (CCG), the Rome workshop, and St Jude Total Therapy Study XI. By life table analysis, 70% to 78% of patients with a favorable prognosis would remain in continuous complete remission (CCR) at 4 years if treated with HDMTX. Uniformly lower CCR rates could be expected with RTSC, especially in St Jude better-risk patients. HDMTX also would show greater efficacy than RTSC in the CCG average-risk and POG poor-risk groups, but the results appear inferior to those being achieved with intensified regimens for high-risk leukemia. Although both therapies would provide adequate CNS prophylaxis in favorable-risk groups, RTSC would offer greater protection in patients classified as being in a worse-risk group by St Jude criteria. We conclude that HDMTX- based therapy, as described in this report, would be most effective in patients with a presenting leukocyte count of less than 25 x 10(9)/L, of the white race, aged 2 to 10 years, and having leukemic cell hyperdiploidy without translocations.

scholarly journals Silencing of Exosomal miR-181a reverses Pediatric Acute Lymphocytic Leukemia Cell Proliferation

2020 ◽  
Author(s):  
Shabirul Haque ◽  
Sarah R. Vaiselbuh
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Cell Lines ◽  
Acute Lymphocytic Leukemia ◽  
Biological Fluids ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Ki 67 ◽  
The Impact

AbstractExosomes are cell-generated nano-vesicles (30-150 nm) found in most biological fluids. Major components of their cargo are lipids, proteins, RNA, DNA, and non-coding RNAs. Exosomes carry the fingerprint of the parental tumor and as such, may regulate tumor growth, progression and metastasis. We investigated the impact of exosomes on cell proliferation in pediatric acute lymphocytic leukemia and its reversal by silencing of exo-miR-181a.We isolated exosomes from serum of acute lymphocytic leukemia pediatric patients (Exo-PALL) and conditioned medium of leukemic cell lines (Exo-CM) by ultracentrifugation. Gene expression was carried out by q-PCR. We found that Exo-PALL promote cell proliferation in leukemic B cell lines as well as in the control B cell line. This exosome-induced cell proliferation is a precise event with up-regulation of proliferative (PCNA, Ki-67) and pro-survival genes (MCL-1, and BCL2), and suppression of pro-apoptotic genes (BAD, BAX). Exo-PALL and Exo-CM both show over expression of miR-181a compared to controls (Exo-HD). Specific silencing of exosomal miR-181a using a miR-181a inhibitor confirms that miR-181a inhibitor treatment reverses Exo-PALL/Exo-CM-induced leukemic cell proliferation in vitro. Altogether, this study suggests that exosomal miR-181a inhibition can be a novel target for growth suppression in pediatric lymphatic leukemia.

scholarly journals Influence of cytotoxicity enhancers in combination with human serum on the activity of CD22-recombinant ricin A against B cell lines, chronic and acute lymphocytic leukemia cells

Leukemia ◽  
1999 ◽  
Vol 13 (2) ◽  
pp. 241-249 ◽  
Author(s):  
PJ van Horssen ◽  
YVJM van Oosterhout ◽  
S Evers ◽  
HHJ Backus ◽  
MGCT van Oijen ◽  
...  
Keyword(s):  
B Cell ◽  
Human Serum ◽  
Cell Lines ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Ricin A

A 14q+ chromosome in a B-cell acute lymphocytic leukemia and in a leukemic non-endemic Burkitt lymphoma

1979 ◽  
Vol 23 (5) ◽  
pp. 639-647 ◽  
Author(s):  
R. M. Slater ◽  
P. Philip ◽  
E. Badsberg ◽  
H. Behrendt ◽  
N. E. Hansen ◽  
...  
Keyword(s):  
B Cell ◽  
Burkitt Lymphoma ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia

scholarly journals A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL)

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1787-1794 ◽  
Author(s):  
Urban Novak ◽  
Elisabeth Oppliger Leibundgut ◽  
Jörg Hager ◽  
Dominique Mühlematter ◽  
Martine Jotterand ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Lymphocytic Leukemia ◽  
Accurate Information ◽  
Trisomy 12 ◽  
Cell Chronic Lymphocytic Leukemia

The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.

scholarly journals Monosomy 12 and deletion of 13q34 in a case of chronic lymphocytic leukemia with concomitant lung cancer

2010 ◽  
Vol 67 (10) ◽  
pp. 864-866 ◽  
Author(s):  
Darko Antic ◽  
Marija Dencic-Fekete ◽  
Dragica Tomin ◽  
Irena Djunic
Keyword(s):  
Lung Cancer ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lung Carcinoma ◽  
Prognostic Significance ◽  
Specific Treatment ◽  
Lymphocytic Leukemia ◽  
Simultaneous Occurrence ◽  
Hybridization Technique

Background. We described a patient with chronic lymphocytic leukemia (CLL) and lung cancer and unusual chromosomal aberrations. Case report. At the same time with the diagnosis of B-cell CLL, squamocellular lung carcinoma diagnosis was established. Using interphase fluoresecence in situ hybridization technique (FISH) we detected monosomy 12 and deletion of 13q34 occured in the same clone. One month after the beginning of examination the patient died unexpectedly during sleep immediately before we applied a specific treatment for CLL or lung carcinoma. Conclusion. Simultaneous occurrence of monosomy 12 and deletion of 13q34 in a patient with B-cell CLL has been described only once before, but as a part of a complex karyotype. The prognostic significance of these abnormalities remains uncertain.

Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia

2000 ◽  
Vol 18 (3) ◽  
pp. 547-547 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Terry L. Smith ◽  
Jorge Cortes ◽  
Francis J. Giles ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Disease ◽  
Adult Acute Lymphocytic Leukemia ◽  
Intensive Regimen

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

scholarly journals Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 340-344 ◽  
Author(s):  
L Baldini ◽  
R Mozzana ◽  
A Cortelezzi ◽  
A Neri ◽  
F Radaelli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Clinical Prognosis ◽  
Delta Type ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu- type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

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