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NCI CANCERLIT® Search: Chronic Myelogenous Leukemia - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11818672
AU - Saydam G; Bozkurt D; Sahin F; Yuksel S; Hekimgil M; Omay SB; Buyukkececi
TI -
F
Acral sclerosis due to interferon-alpha-2b in chronic myelogenous
leukemia.
SO - Acta Haematol 2002;107(1):43-5
AD - Department of Hematology, School of Medicine, Ege University, TR-35100
Bornova, Izmir, Turkey. gsaydam@med.ege.edu.tr
2
UI - 11870560
AU - Hochhaus A
TI -
[Selective tyrosine kinase inhibitor imatinib (STI571) in haematological
and oncological disease]
SO - Dtsch Med Wochenschr 2002 Mar 1;127(9):451-6
AD - III. Medizinische Universitatsklinik, Fakultat fur Klinische Medizin
Mannheim der Universitat Heidelberg, Germany. hochhaus@uni-hd.de
3
UI - 11760557
AU - Wetzler M; NCCN Chronic Myelogenous Leukemia Practice Guidelines Panel
TI -
NCCN: Chronic myelogenous leukemia.
SO - Cancer Control 2001 Nov-Dec;8(6 Suppl 2):44-8
4
UI - 11868361
AU - Sano H; Kikuta A; Ito M; Nemoto K; Hojo H; Ohto H
TI -
[Successful treatment with combined anti-thymocyte globulin and
methylprednisolone for bronchiolitis obliterans after allogeneic bone
marrow transplantation in a child with chronic myelogenous leukemia]
SO - Rinsho Ketsueki 2002 Jan;43(1):23-8
AD - Department of Pediatrics, Fukushima Medical University School of
Medicine.
A 9-year-old boy with secondary chronic myelogenous leukemia after
treatment of acute lymphoblastic leukemia underwent allogeneic bone
marrow transplantation (BMT) from an HLA-identical sibling in December
1998. Grade II acute GVHD developed on day 24 and chronic GVHD developed
5 months after BMT. Cough and dyspnea appeared 9 months after BMT.
Despite administration of tacrolimus and methylprednisolone (m-PSL)
pulse therapy, the dyspnea gradually increased in severity.
Bronchiolitis obliterans was diagnosed on the basis of lung biopsy in
the use of tacrolimus, we attempted antithymocyte globulin (ATG) + m-PSL
therapy. Major BCR/ABL mRNA was transiently positive on RT-PCR after the
ATG + m-PSL therapy, but no severe complications were observed. A
decreasing V50/V25 level and increasing peak flow value were observed in
respiratory function tests after ATG + m-PSL therapy, and the patient is
currently free of dyspnea. Our findings suggest that ATG + m-PSL therapy
is beneficIal for patients with drug-resistant bronchiolitis obliterans
after BMT.
5
UI - 11896544
AU - Langabeer SE; Gale RE; Harvey RC; Cook RW; Mackinnon S; Linch DC
TI -
Transcription-mediated amplification and hybridisation protection assay
to determine BCR-ABL transcript levels in patients with chronic myeloid
leukaemia.
SO - Leukemia 2002 Mar;16(3):393-9
AD - Department of Haematology, University College London, London, UK.
Detection of BCR-ABL transcripts in chronic myeloid leukaemia (CML) is
used to confirm the diagnosis and to monitor residual disease.
Quantitative techniques are required to predict response to therapy or
early relapse. We have evaluated an assay in which
transcription-mediated amplification (TMA) of BCR-ABL and ABL
transcripts is achieved using reverse transcriptase and RNA polymerase.
The products are quantified in the hybridisation protection assay (HPA)
using acridinium ester-labelled DNA probes and chemiluminescence. The
method is a single tube procedure which uses small amounts of RNA (<500
ng/triplicate analysis), is technically simple (requiring just two
waterbaths and a luminometer), rapid (total assay time <4 h) and
sensitive (capable of detecting one BCR-ABL-positive K562 cell in the
presence of 10(4)-10(5) BCR-ABL-negative cells). BCR-ABL signals from
patient RNA samples were quantified relative to known amounts of K562
RNA and normalised to levels of ABL. BCR-ABL/ABL ratios ranged from 0.15
to 1.59 (median 0.65) in RNA from diagnostic blood or bone marrow of 18
CML patients and were < or =0.0001 in 20 normal controls. Sequential
samples analysed from six CML patients post-allogeneic bone marrow
transplantation who relapsed and received donor lymphocyte infusions
showed BCR-ABL/ABL ratios which reflected patient status or treatment. A
BCR-ABL/ABL ratio of 0.01 served as a useful arbitrary indicator value,
with results above and below this value generally correlating with
relapse or remission, respectively.
6
UI - 11801476
AU - Castelli R; Faricciotti A; Cicuti S; Franceschini F; Vismara A; Porro T
TI -
Acquired factor VIII inhibitor in association with myelodisplastic
syndrome: report of a new case.
SO - Haematologica 2002 Jan;87(1):ECR02
AD - U.O. di Medicina Interna II, Azienda Ospedaliera G. Salvini, Presidio
Ospedaliero di Rho, Corso Europa 250-20017 Rho, Milan, Italy.
castelli39@interfree.it
7
UI - 11849238
AU - Smith FO; King R; Nelson G; Wagner JE; Robertson KA; Sanders JE; Bunin
TI -
N; Emaunel PD; Davies SM; The National Marrow Donor Program
Unrelated donor bone marrow transplantation for children with juvenile
myelomonocytic leukaemia.
SO - Br J Haematol 2002 Mar;116(3):716-24
AD - Division of Hematology/Oncology, Children's Hospital Medical Center,
Cincinnati, OH 45229, USA. frank.smith@chmcc.org
Children with juvenile myelomonocytic leukaemia (JMML) have a poor
outcome, with survival in a minority of patients. The major limitation
on success of sibling donor bone marrow transplantation for JMML has
been reported to be relapse. A total of 46 children with a diagnosis of
JMML underwent unrelated donor marrow (URD) transplantation facilitated
by the National Marrow Donor Program. Forty-three of 46 patients had
neutrophil engraftment at a median of 20 d post transplant, with
platelet recovery in 28 of 40 evaluable patients at a median of 34.5 d.
Thirty-two of 44 evaluable patients developed acute
graft-versus-host-disease (GVHD) (Grades 2-4) and chronic GVHD developed
in 14 of 35 evaluable patients. At a median follow-up of 2.0 years,
probabilities of survival and disease-free survival were 42% and 24%
respectively. The probability of relapse was 58% at 2 years and
represents the major cause of treatment failure. Multivariate analysis
revealed that chronic GVHD was associated with reduced relapse [risk
ratio 0.20 (95% CI 0.04-1.02, P=0.05)] improved survival [risk ratio
0.13 (95% CI 0.03-0.68, P=0.02)] and event-free survival [risk ratio
0.23 (95% CI 0.06-0.94, P=0.04)]. This study demonstrates that relapse
is the major cause of treatment failure in patients with JMML undergoing
URD transplantation. With lower relapse observed in patients with
chronic GVHD, new treatment strategies that focus on enhancing the
graft-versus-leukaemia effect may improve survival.
8
UI - 11894916
AU - Wiedemann L M; Burns J H; Birnie G D
TI -
Differences among the polyadenylated RNA sequences of human leucocyte
populations: an approach to the objective classification of human
leukaemias.
SO - EMBO J 1983;2(1):9-13
AD - The Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
We have constructed a complementary DNA (cDNA) library representing
expressed sequences of the white blood cells from a patient with chronic
granulocytic leukaemia. The library was screened by colony hybridization
of 32P-labelled cDNAs synthesized from the polyadenylated RNAs of the
white blood cells from patients with chronic granulocytic or chronic
lymphocytic leukaemia. The autoradiographic patterns were compared and
70 recombinants were selected to comprise a panel which distinguished
between these two types of leukaemia. Hybridization of this panel with
complementary DNAs transcribed from the polyadenylated RNAs of a variety
of normal and neoplastic leucocyte populations showed that the RNA
sequences in high abundance in leucocytes from chronic granulocytic
leukaemias differ quite radically from those in other leucocytes. The
patterns of hybridization seen when this panel was challenged with cDNAs
representing the RNAs of normal and leukaemic leucocyte populations were
sufficiently different to distinguish clearly the peripheral blood
leucocytes of chronic granulocytic leukaemias from other populations of
white blood cells, both normal and leukaemic. We suggest that this
approach might provide additional markers useful in the classification
of the acute leukaemias, especially the undifferentiated leukaemias
whose identification by conventional methods is uncertain.
9
UI - 11905596
AU - Anonymous
TI -
Is red tape stifling the progress of new anticancer drugs?
SO - Lancet Oncol 2002 Jan;3(1):1
10
UI - 11905608
AU - Habeck M
TI -
FDA licences imatinib mesylate for CML.
SO - Lancet Oncol 2002 Jan;3(1):6
11
UI - 11920509
AU - Verstovsek S; Kantarjian H; Manshouri T; O'Brien S; Faderl S; Talpaz M;
TI -
Cortes J; Albitar M
Prognostic significance of Tie-1 protein expression in patients with
early chronic phase chronic myeloid leukemia.
SO - Cancer 2002 Mar 1;94(5):1517-21
AD - Department of Leukemia, University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030, USA.
BACKGROUND: The Tie-1 tyrosine kinase receptor and its thus far
unidentified ligand appear to play a distinct role in the regulatory
pathways of early hematopoiesis and angiogenesis. Because vascularity is
increased in the bone marrow of patients with chronic myeloid leukemia
(CML), the authors evaluated the clinical significance of Tie-1
expression in such patients. METHODS: Using Western blot analysis and
solid-phase radioimmunoassay (RIA), the authors quantified Tie-1 protein
in bone marrow samples from 128 patients with CML and 31 normal
controls. RESULTS: The median Tie-1 RIA value of CML samples was
significantly higher than in normal controls (P = 0.01). The authors
found no significant differences in Tie-1 levels in patients with early
chronic, late chronic, accelerated, and blastic phases (P = 0.2). High
Tie-1 levels correlated with short survival in patients with early
chronic phase (P = 0.003; Cox proportional hazard model) but not in
patients with late chronic (P = 0.2) or accelerated/blastic (P = 0.2)
phase CML. Tie-1 protein level was also prognostic when patients were
separated into two groups by the median value. High Tie-1 level in early
chronic phase was associated with significantly shorter survival than
low Tie-1 level (median survival, 116 vs. 61 months; P = 0.03). In
patients with early chronic phase CML, Tie-1 levels correlated directly
with patient age (P = 0.004) and platelet count (P = 0.003), and
inversely with leukocyte count (P = 0.007). Tie-1 as a predictor of
survival in early chronic phase CML was independent of risk group,
spleen size, age, hemoglobin, and basophil count (P = 0.03; multivariate
Cox proportional hazard model). CONCLUSIONS: The authors' findings
support the hypothesis that angiogenesis may play a major role in the
pathophysiology of chronic phase CML. Copyright 2002 American Cancer
Society.
12
UI - 11171837
AU - Monteleone G; Pender SL; Alstead E; Hauer AC; Lionetti P; McKenzie C;
TI -
MacDonald TT
Role of interferon alpha in promoting T helper cell type 1 responses in
the small intestine in coeliac disease.
SO - Gut 2001 Mar;48(3):425-9
AD - Division of Infection, Allergy, Inflammation, and Repair, University of
Southampton School of Medicine, Southampton General Hospital,
Southampton, UK.
Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1)
response in the small intestinal mucosa to dietary gluten. As the major
Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa,
the mechanism by which Th1 effector cells are generated remains unknown.
Interferon (IFN) alpha, a cytokine capable of promoting IFN-gamma
synthesis, has been implicated in the development of Th1 mediated immune
diseases. Here we report a case of CD-like enteropathy in a patient
receiving IFN-alpha for chronic myeloid leukaemia. Morphological
assessment of duodenal biopsies taken from the patient showed total
villous atrophy, crypt cell hyperplasia, and a high number of CD3+
intraepithelial lymphocytes. Both antigliadin antibodies and
antiendomysial antibodies were positive. RNA analysis revealed
pronounced expression of IFN-gamma. Withdrawal of gluten from the diet
resulted in a patchy improvement in intestinal morphology, normalisation
of laboratory parameters, and resolution of clinical symptoms. By
western blot analysis, IFN-alpha protein was seen in the duodenal mucosa
from untreated CD patients but not in controls. This was associated with
marked expression of IFN-gamma protein in CD mucosa. Collectively, these
results suggest a role for IFN-alpha in promoting Th1 responses to
gluten.
13
UI - 11892878
AU - McLaren BK; Muldoon R; Veillon DM; Nordberg ML; Weinberger B; Cotelingam
TI -
JD
Unexpected leukocytosis in a preoperative patient.
SO - J La State Med Soc 2002 Jan-Feb;154(1):17-9
AD - Department of Pathology, Louisiana State University Health Sciences
Center, Shreveport, USA.
14
UI - 11836164
AU - La Starza R; Testoni N; Lafage-Pochitaloff M; Ruggeri D; Ottaviani E;
TI -
Perla G; Martelli MF; Marynen P; Mecucci C
Complex variant Philadelphia translocations involving the short arm of
chromosome 6 in chronic myeloid leukemia.
SO - Haematologica 2002 Feb;87(2):143-7
AD - Hematology and Bone Marrow Transplantation Unit, University of Perugia,
Italy.
BACKGROUND AND OBJECTIVES: Around 5% of chronic myeloid leukemias (CML)
are characterized by complex variant Philadelphia (Ph) translocations
involving one or more chromosomal regions in addition to 9 and 22. The
BCR/ABL1 fusion gene is usually found on der(22). The additional gene(s)
involved in complex variant Ph rearrangements have not been
characterized. DESIGN AND METHODS: We performed fluorescent in situ
hybridization (FISH) in three complex variant Ph translocations
involving the short arm of chromosome 6 in addition to 9 and 22. The
BCR/ABL1 D-FISH probe was applied to localize the BCR/ABL1 fusion gene
as well as the 5'ABL1 and the 3'BCR. Locus-specific probes were used to
narrow the 6p breakpoint. RESULTS: In all cases the BCR/ABL1 fusion gene
was located on the Ph chromosome whereas the reciprocal ABL1/BCR gene
was detected only in patient #2. On 6p, breakpoints were narrowed to
three different regions: centromeric to the human major
histocompatibility complex (MHC), between PAC 524E15 and PAC162J16, in
the first patient, and telomeric to the MHC, between PAC 329A5 and PAC
145H9, and between PAC 136B1 and PAC 206F19, in the second and third
patients, respectively. In patients #2 and 3 a chromosomal rearrangement
different from a true complex variant was discovered. In both cases, a
classical t(9;22) was associated with an additional translocation
involving the der(9)t(9;22). INTERPRETATION AND CONCLUSIONS:
Rearrangements at 6p in complex Ph aberrations involve more than one
gene/locus. Classical t(9;22), masked by additional chromosomal
rearrangements, can resemble complex variant Ph translocations, and can
be detected only using appropriate FISH probes.
15
UI - 11907793
AU - Martel L; Reddy K; Greco M; Tuscano M; Richman M; Wun T
TI -
Isolated cavernous sinus extramedullary relapse of chronic myelogenous
leukemia following allogeneic stem cell transplant.
SO - Ann Hematol 2002 Feb;81(2):108-10
AD - Division of Hematology and Oncology, Department of Internal Medicine,
University of California, Davis, Medical Center, 4501 X Street,
Sacramento, CA 95817, USA. calucd@msn.com
Isolated extramedullary relapse of chronic myelogenous leukemia (CML)
after allogeneic stem cell transplant is rare. A case is reported of a
patient who developed a granulocytic sarcoma of the cavernous sinus 7
months after allogeneic transplant for CML. He presented with neurologic
deficits, and a mass lesion was found on imaging. No evidence of
hematologic relapse was identified by bone marrow histology or
cytogenetics. A premortem diagnosis was not possible, and the patient
died 2 months later of an intracerebral hemorrhage after receiving
various therapies directed against a presumed infectious etiology.
Granulocytic sarcoma should be considered in the differential diagnosis
of mass lesions presenting after allogeneic transplant for CML, even if
there is no evidence of medullary disease.
16
UI - 7718887
AU - Diamond J; Goldman JM; Melo JV
TI -
BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual
granulocyte-macrophage colony-forming unit colonies derived from blood
of patients with chronic myeloid leukemia.
SO - Blood 1995 Apr 15;85(8):2171-5
AD - Department of Haematology, Royal Postgraduate Medical School, London,
UK.
It has been suggested that the BCR-ABL gene of chronic myeloid leukemia
(CML) is not uniformly expressed in Philadelphia (Ph)-positive cells,
and that BCR-ABL gene expression precludes transcription of the normal
BCR or ABL genes. Therefore, we have analyzed granulocyte-macrophage
colony-forming unit (CFU-GM) colonies derived from peripheral blood of
11 CML patients by cytogenetic and by reverse transcriptase-polymerase
chain reaction (PCR) amplification of BCR-ABL, ABL-BCR, BCR, and ABL.
All CFU-GM colonies with analyzable metaphases were found to contain a
Ph chromosome. In 2 patients, the initial PCR screening failed to detect
BCR-ABL transcripts in 2 of 11 and 1 of 7 Ph-positive colonies. However,
when amplification for BCR-ABL was repeated in quintuplicate, all but 1
colony from a single patient showed one or more positive results.
Amplifications of the four genes in each colony showed that BCR-ABL,
ABL-BCR, and the normal BCR and ABL were simultaneously expressed in the
majority of CFU-GM colonies. Replicate PCR tests for BCR and for ABL in
colonies initially scored as negative also uncovered previously
undetected positive amplifications. We conclude that BCR-ABL expression
does not suppress transcription from the normal BCR and ABL genes, and
that Ph-positive, BCR-ABL-negative colonies derived from peripheral
blood CFU-GM are rare or nonexistent.
17
UI - 11535505
AU - Huntly BJ; Reid AG; Bench AJ; Campbell LJ; Telford N; Shepherd P; Szer
TI -
J; Prince HM; Turner P; Grace C; Nacheva EP; Green AR
Deletions of the derivative chromosome 9 occur at the time of the
Philadelphia translocation and provide a powerful and independent
prognostic indicator in chronic myeloid leukemia.
SO - Blood 2001 Sep 15;98(6):1732-8
AD - Department of Hematology, University of Cambridge, Cambridge, United
Kingdom.
Chronic myeloid leukemia (CML) is characterized by formation of the
BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph)
translocation between chromosomes 9 and 22. Large deletions on the
derivative chromosome 9 have recently been reported, but it was unclear
whether deletions arose during disease progression or at the time of the
Ph translocation. Fluorescence in situ hybridization (FISH) analysis was
used to assess the deletion status of 253 patients with CML. The
strength of deletion status as a prognostic indicator was then compared
to the Sokal and Hasford scoring systems. The frequency of deletions was
similar at diagnosis and after disease progression but was significantly
increased in patients with variant Ph translocations. In patients with a
deletion, all Ph(+) metaphases carried the deletion. The median survival
of patients with and without deletions was 38 months and 88 months,
respectively (P =.0001). By contrast the survival difference between
Sokal or Hasford high-risk and non-high-risk patients was of only
borderline significance (P =.057 and P =.034). The results indicate that
deletions occur at the time of the Ph translocation. An apparently
simple reciprocal translocation may therefore result in considerable
genetic heterogeneity ab initio, a concept that is likely to apply to
other malignancies associated with translocations. Deletion status is
also a powerful and independent prognostic factor for patients with CML.
The prognostic significance of deletion status should now be studied
prospectively and, if confirmed, should be incorporated into management
decisions and the analysis of clinical trials.
18
UI - 8524841
AU - Raitano AB; Halpern JR; Hambuch TM; Sawyers CL
TI -
The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for
transformation.
SO - Proc Natl Acad Sci U S A 1995 Dec 5;92(25):11746-50
AD - Department of Medicine, University of California, Los Angeles, School of
Medicine 90095-1678, USA.
The leukemogenic tyrosine kinase fusion protein Bcr-Abl activates a
Ras-dependent pathway required for transformation. To examine subsequent
signal transduction events we measured the effect of Bcr-Abl on two
mitogen-activated protein kinase (MAPK) cascades--the extracellular
signal-regulated kinase (ERK) pathway and the Jun N-terminal kinase
(JNK) pathway. We find that Bcr-Abl primarily activates JNK in
fibroblasts and hematopoietic cells. Bcr-Abl enhances JNK function as
measured by transcription from Jun responsive promoters and requires
Ras, MEK kinase (MAPK/ERK kinase kinase), and JNK to do so.
Dominant-negative mutants of c-Jun, which inhibit the endpoint of the
JNK pathway, impair Bcr-Abl transforming activity. These findings
implicate the JNK pathway in transformation by a human leukemia
oncogene.
19
UI - 8882929
AU - Anonymous
TI -
Antisense gene therapy trials underway in patients with CML.
SO - Oncology (Huntingt) 1996 Sep;10(9):1411
20
UI - 10079288
AU - Thorpe KL; Schafer AJ; Genin E; Trowsdale J; Beck S
TI -
Detection of polymorphism in the RING3 gene by high-throughput
fluorescent SSCP analysis.
SO - Immunogenetics 1999 Apr;49(4):256-65
AD - The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge,
CB10 1SA, UK.
We describe the use of a high-throughput, fluorescent,
polymorphism-detection system, based on single-strand conformation
polymorphism to screen for polymorphism in the RING3 gene. This is the
first extensive mutation screen of this major histocompatibility
complex-linked gene, and the entire coding region and intron-exon
junctions were examined by multiplexing over 3000 polymerase chain
reaction products. These techniques should be applicable for analysis of
variation in other human genes. Investigation of DNA from acute
lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML)
patients, as well as healthy individuals revealed low levels of
polymorphism across the RING3 gene. Comparison of the distribution of
genotypes at each polymorphic site between patients and healthy
individuals revealed a single site which significantly deviates from
Hardy-Weinberg proportions.
21
UI - 11843913
AU - Rodriguez-Gomez F; Cuevas O; Anguita J; Munoz P
TI -
Clinical microbiological case: penile ulcer and lung infiltrates in a
leukemic patient.
SO - Clin Microbiol Infect 2001 Dec;7(12):695-6, 713-4
AD - Clinical Microbiology and Hematology Departments, Hospital General
Universitario Gregorio Maranon, Madrid, Spain.
22
UI - 11237056
AU - Creutzig U; Ritter J; Zimmermann M; Hermann J; Gadner H; Sawatzki DB;
TI -
Niemeyer CM; Schwabe D; Selle B; Boos J; Kuhl J; Feldges A
Idarubicin improves blast cell clearance during induction therapy in
children with AML: results of study AML-BFM 93. AML-BFM Study Group.
SO - Leukemia 2001 Mar;15(3):348-54
AD - University Children's Hospital, Department of Hematology/Oncology,
Munster, Germany.
In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin
with 12 mg/m2/day idarubicin for 3 days each, combined with cytarabine
and etoposide during induction. Results showed a significant better
blast cell reduction in the bone marrow on day 15 in patients of the
idarubicin arm (25 of 144 = 17% of patients with > or = 5% blasts
compared to 46 of 149 = 31% of patients after daunorubicin, Pchi2 =
0.01). This was, however, mainly seen in high risk patients treated with
idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1-3
shortening fraction reduction after induction occurred in 6% patients in
both arms. Bone marrow toxicity differed slightly with a median recovery
time of neutrophils >500/microl of 25 days (daunorubicin) compared to 27
days (idarubicin), P = 0.05. In the total group of patients
probabilities of 5 years event-free survival and disease-free survival
were similar for patients treated with daunorubicin or idarubicin (49%
+/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64% +/- 4%, P logrank 0.29 and
0.15, respectively). However, in patients presenting with more than 5%
blasts on day 15 there was a trend for a better outcome after treatment
with idarubicin (P logrank 0.06). Together with the early effect seen
for high risk patients these results indicate a better efficacy of
idarubicin than of daunorubicin during induction with a similar rate of
toxicity.
23
UI - 11917947
AU - Radojkovic M; Ristic S; Colovic M; Todoric B; Krtolica K
TI -
Busulfan-induced loss of Ph chromosome in chronic myeloid leukemia.
SO - Med Oncol 2001;18(3):227-9
AD - Clinic of Internal Medicine, Clinical Center Dr Dragisa Misovic,
Belgrade, Yugoslavia. radojkov@EUnet.yu
We report a 44-yr-old female with Philadelphia chromosome positive
chronic myeloid leukemia who was initially treated with busulfan, and
clinical remission has been achieved. After 4 yr, low-dose busulfan
therapy was started again and induced bone marrow aplasia. The patient
spontaneously has recovered from aplasia, and complete cytogenetic
remission with loss of Ph+ chromosome in bone marrow has been achieved.
However, reverse-transcription-polymerase chain reaction analysis showed
presence of the bcr-abl transcript in bone marrow.
24
UI - 11697340
AU - de la Fuente J; Merx K; Steer EJ; Muller M; Szydlo RM; Maywald O; Berger
TI -
U; Hehlmann R; Goldman JM; Cross NC; Melo JV; Hochhaus A; The German CML
Study Group
ABL-BCR expression does not correlate with deletions on the derivative
chromosome 9 or survival in chronic myeloid leukemia.
SO - Blood 2001 Nov 1;98(9):2879-80
25
UI - 11830457
AU - Elmaagacli AH; Basoglu S; Peceny R; Trenschel R; Ottinger H; Lollert A;
TI -
Runde V; Grosse-Wilde H; Beelen DW; Schaefer UW
Improved disease-free-survival after transplantation of peripheral blood
stem cells as compared with bone marrow from HLA-identical unrelated
donors in patients with first chronic phase chronic myeloid leukemia.
SO - Blood 2002 Feb 15;99(4):1130-5
AD - Department of Bone Marrow Transplantation, Institute of Immunology,
University Hospital of Essen, Germany. ahmet.elmaagacli@uni-essen.de
Outcomes after peripheral blood stem cell transplantation (PBSCT) for
chronic phase chronic myeloid leukemia (n = 37) were compared with
outcomes after bone marrow transplantation (BMT) (n = 54) in the
HLA-compatible unrelated donor setting. Median follow-up was 17 months
after PBSCT and 29 months after BMT. Both neutrophil and platelet
recovery were faster after PBSCT (P <.05). PBSCT was associated with
improved immune reconstitution, with higher peripheral blood naive
(CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3
months and 12 months after transplantation (P <.03). The cumulative
incidence of acute (grades II-IV) and chronic graft-versus-host disease
(GVHD) were similar, but BMT was associated with a higher cumulative
incidence of severe, acute (grade III-IV) GVHD at 24% as compared with
8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive
positive polymerase chain reaction assays for bcr-abl within a 4-week
interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in
4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse
occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%)
patients after PBSCT (not significant). Seventeen of the 54 patients
died after BMT (31%), as compared with 2 of 37 patients after PBSCT
(5%). Deaths in the BMT group were associated mainly with infections and
severe, acute GVHD. The estimated probability of transplant-related
mortality (TRM) and disease-free survival at 1000 days after receiving
the transplant were 30% and 64% in the BMT group and 5% and 91% in the
PBSCT group (P <.03). Overall survival 1000 days after receiving the
transplant was 66% after BMT and 94% after PBSCT (P <.02). In the
multivariate analysis, only acute GVHD significantly influenced TRM (P
<.01).
26
UI - 11111454
AU - Zitella L
TI -
Tyrosine kinase inhibitors: a cure for chronic myeloid leukemia?
SO - Clin J Oncol Nurs 2000 Sep-Oct;4(5):227-9
AD - Stanford Hospital and Clinics, 300 Pasteur Drive H1353, Stanford, CA
94305, USA. lzitella@yahoo.com
Chronic myeloid leukemia (CML), a malignant transformation of
hematopoietic cells, accounts for one-fifth of all leukemias and will be
diagnosed in 4,400 individuals in the United States this year. CML has
three phases: chronic, accelerated, and blastic. Interferon,
hydroxyurea, busulfan, and bone marrow and stem cell transplantation are
used to treat CML, but individuals who are in the accelerated phases or
blast crisis usually respond poorly to treatment. A new tyrosine kinase
inhibitor, STI 571, is being evaluated in clinical trials. STI 571 is
highly bioavailable in oral form and produced minimal toxicities in
phase I studies. Further research is needed to determine the rate of
response and survival data, but STI 571 holds great promise in the
treatment of CML.
27
UI - 11925871
AU - Kakihana K; Mizuchi D; Yamaguchi M; Sakashita C; Fukuda T; Yamamoto K;
TI -
Miki T; Tohda S; Koyama T; Murakami N; Miura O
[Hypercalcemia mediated by parathyroid hormone-related protein in the
blastic phase of chronic myelogenous leukemia]
SO - Rinsho Ketsueki 2002 Feb;43(2):102-6
AD - Department of Hematology and Oncology, Tokyo Medical and Dental
University.
A 45-year-old man with chronic myelogenous leukemia (CML) in the
accelerated phase was admitted to our hospital because of lower back
pain and hypercalcemia. On admission, he was confused and found to have
massive splenomegaly. The hypercalcemia and splenomegaly improved
significantly after administration of incadronate, hydroxyurea,
vincristine and prednisolone. Splenomegaly recurred after cessation of
the chemotherapy, and examination of the peripheral blood showed 31%
blasts, positive for both CD13 and CD33, on which basis myeloid blastic
transformation was diagnosed. Vindesine, cytarabine and prednisolone
were administered, and the splenomegaly improved again. On admission,
when the patient's serum calcium level was 16.0 mg/dl, his serum
parathyroid hormone-related protein (PTHrP) level was elevated to 118.3
pmol/l. Furthermore, RT-PCR analysis revealed that the patient's CML
cells expressed PTHrP mRNA, and a high level of PTHrP was detected in
the supernatant of cultured mononuclear cells derived from the patient's
peripheral blood. These findings indicated that the hypercalcemia was
due to production of PTHrP by the leukemic cells. Several cases of
PTHrP. mediated hypercalcemia associated with CML have been reported
previously, and are reviewed here.
28
UI - 11932905
AU - O'Brien S; Talpaz M; Cortes J; Shan J; Giles FJ; Faderl S; Thomas D;
TI -
Garcia-Manero G; Mallard S; Beth M; Koller C; Kornblau S; Andreeff M;
Murgo A; Keating M; Kantarjian HM
Simultaneous homoharringtonine and interferon-alpha in the treatment of
patients with chronic-phase chronic myelogenous leukemia.
SO - Cancer 2002 Apr 1;94(7):2024-32
AD - Department of Leukemia and Bioimmunotherapy, M. D. Anderson Cancer
Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
BACKGROUND: Homoharringtonine (HHT) has antileukemic activity in
patients with Philadelphia chromosome (Ph) positive chronic myelogenous
leukemia (CML). Combinations of HHT, interferon-alpha (IFN-alpha), and
cytarabine (ara-C) have been studied in various CML phases. The
objectives of this study were to evaluate the efficacy and toxicity
profiles of a combination regimen of simultaneous HHT and IFN-alpha
therapy in patients with chronic-phase CML who were not exposed
previously to either agent. METHODS: Forty-seven patients were treated:
37 patients with early chronic-phase CML (2 patients with clonal
evolution) and 10 patients with late chronic-phase CML. Their median age
was 62 years (range, 23-73 years). HHT was given at a dose of 2.5
mg/m(2) by continuous intravenous infusion over 24 hours daily for 5
days every month, and IFN-alpha was given daily at a target dose of 5 x
10(6) units/m(2) subcutaneously. Response, survival, and treatment
toxicity were analyzed. RESULTS: Overall, the complete hematologic
response (CHR) rate was 85%; the cytogenetic response rate was 66%, with
major cytogenetic responses (Ph positive in < 35% of metaphases) in 49%
of patients and complete cytogenetic responses in 21% of patients. The
CHR rate, cytogenetic response rate, and major cytogenetic response rate
were 84%, 69%, and 52%, respectively, in patients with early
chronic-phase CML. Among the 10 patients with late chronic-phase CML,
the CHR rate, cytogenetic response rate, and major cytogenetic response
rate were 80%, 50%, and 40%, respectively. Response rates in patients
age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and
major cytogenetic response. Myelosuppression was frequent but
manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of
patients, requiring dose adjustments and erythropoietin therapy.
Nonhematologic toxicities were mainly fatigue, aches, and
gastrointestinal disturbances. Dose reductions with multiple courses
were significant and were due to myelosuppression: After 6-24 courses,
the median daily IFN-alpha dose was 1 MU/m(2), and the median number of
days on HHT per month was 2 days. With a median follow-up of 26 months,
the estimated 2-year survival rate was 90% (95% confidence interval,
79-100%). CONCLUSIONS: The simultaneous combination of HHT and IFN-alpha
is safe and effective, but the dose schedules that actually were
delivered were significantly lower than the planned dose schedules. With
the availability of signal-transduction inhibitor 571 (imatinib
mesylate), studies of combination of HHT and IFN-alpha chemotherapy in
patients with CML who have disease that fails to respond to imatinib
mesylate and of combinations with imatinib mesylate need to be explored.
Copyright 2002 American Cancer Society.
29
UI - 11818460
AU - Nowell PC
TI -
Progress with chronic myelogenous leukemia: a personal perspective over
four decades.
SO - Annu Rev Med 2002;53():1-13
AD - Department of Pathology and Laboratory Medicine, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
nowell@mail.med.upenn.edu
Our understanding and treatment of chronic myelogenous leukemia (CML)
has progressed since 1960 in parallel with work on cancer in general.
CML provided the first evidence of a specific genetic change associated
with a human cancer (the Philadelphia chromosome) and the clonal nature
of these disorders. With improved cytogenetic and molecular techniques
over subsequent decades, the specific genetic rearrangements of CML and
many other tumors were defined and the complex mechanisms of
carcinogenesis gradually unraveled. During this period, improved
treatments for CML (chemotherapy, interferon, bone marrow
transplantation) were implemented, and therapy targeted to the specific
genetic change in the leukemic cells has recently been brought to
promising clinical trials. Similar efforts are under way for other human
cancers, and although the problem is enormously complex, there is real
hope for major improvements in controlling these disorders.
30
UI - 11818480
AU - O'Dwyer ME; Mauro MJ; Druker BJ
TI -
Recent advancements in the treatment of chronic myelogenous leukemia.
SO - Annu Rev Med 2002;53():369-81
AD - Leukemia Center, Oregon Cancer Institute, Oregon Health & Science
University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA.
odwyerm@ohsu.edu
Chronic myelogenous leukemia (CML) is a clonal hematopoetic stem cell
disorder characterized by the Philadelphia chromosome and resultant
production of the constitutively activated Bcr-Abl tyrosine kinase.
Characterized clinically by marked myeloid proliferation, it invariably
terminates in an acute leukemia. Conventional therapeutic options
include interferon-based regimens and stem cell transplantation, with
stem cell transplantation being the only curative therapy. Through
rational drug development, STI571, a Bcr-Abl tyrosine kinase inhibitor,
has emerged as a paradigm for gene product targeted therapy, offering
new hope for expanded treatment options for patients with CML.
31
UI - 11945192
AU - Chae SW; Cho JH; Lee JH; Kang HJ; Hwang SJ
TI -
Sudden hearing loss in chronic myelogenous leukaemia implicating the
hyperviscosity syndrome.
SO - J Laryngol Otol 2002 Apr;116(4):291-3
AD - Department of Otolaryngology-Head and Neck Surgery, College of Medicine,
Korea University, Seoul, Korea. chaeorl@kumc.or.kr
Sudden sensorineural hearing loss that presents as the initial sign of
haematological disease is very rare. Chronic myelogenous leukaemia has
been implicated as a causative factor of sudden sensorineural hearing
loss. A 49-year-old male presented with unilateral sudden sensorineural
hearing loss. The patient was found to have chronic myelogenous
leukaemia during a work-up for his hearing loss. We present a case of a
chronic myelogenous leukaemia patient whose first manifestation was
sudden sensorineural hearing loss. We presume that cochlear vessel
occlusion as a result of elevated blood viscosity was responsible for
this patient's hearing loss. Early onset of sudden deafness in a chronic
myelogenous leukaemia patient may be due to the hyperviscosity syndrome
and it may be possible to reverse hearing loss through early
leukapheresis.
32
UI - 11839377
AU - Tripathi AK; Chaturvedi R; Ahmad R; Asim M; Sawlani KK; Singh RL;
TI -
Tekwani BL
Peripheral blood leucocytes ornithine decarboxylase activity in chronic
myeloid leukemia patients: prognostic and therapeutic implications.
SO - Leuk Res 2002 Apr;26(4):349-54
AD - Hemato-oncology Unit, Department of Medicine, K.G.'s Medical College,
Lucknow, India. tripathiak@satyam.net.in
Leukocytes ornithine decarboxylase (ODC) activity was measured in normal
individuals and in patients with chronic myeloid leukemia (CML) in
chronic phase (CML-CP) as well as in accelerated phase (CML-AP), with an
aim to examine the role of ODC activity in prognostic evaluation of CML
patients. Our results showed that ODC activity was significantly higher
in CML-CP (41.02+/-25.57nmol/h per 10(7) cells, P<0.005) and CML-AP
(67.71+/-44.42nmol/h per 10(7) cells, P<0.001) patients than in normal
subjects (3.12+/-1.34nmol/h per 10(7) cells). Furthermore, patients with
CML-AP showed higher ODC activity than CML-CP patients (P<0.005).
Patients with CML-CP who converted to accelerated phase within 24 months
had higher ODC activity (84.58+/-12.81nmol/h per 10(7) cells) than
patients who did not convert to accelerated phase (31.13+/-18.24nmol/h
per 10(7) cells). The high value of ODC activity was also associated
with less clinico-hematological response. We suggest that ODC activity
reflects the neoplastic proliferative activity in CML patients and may
serve as an additional prognostic marker.
33
UI - 11839390
AU - Flamm MJ; Murty VV; Rao PH; Nichols GL
TI -
Coexistence of independent myelodysplastic and Philadelphia chromosome
positive clones in a patient treated with hydroxyurea.
SO - Leuk Res 2002 Apr;26(4):417-20
AD - Department of Medicine, Columbia University College of Physicians and
Surgeons, Herbert Irving Comprehensive Cancer Center, 650 W, 168th
Street BB-20-08, New York, NY, 10032, USA. mjf3@columbia.edu
We report a patient with Philadelphia chromosome positive (Ph +ve)
chronic myelogenous leukemia (CML), treated with hydroxyurea alone, who
upon disease progression developed an additional Ph - ve clone
containing chromosomal abnormalities typical of myelodysplastic syndrome
(MDS). Retrospective analysis of a cryopreserved stem cell specimen from
diagnosis confirmed that this second clone developed during the course
of treatment. The development of a clone with additional cytogenetic
abnormalities in CML has only been reported after leukemogenic
treatment, stem cell transplantation or interferon. We report a case of
secondary Ph - ve MDS/AML during blast crisis in a patient treated with
hydroxyurea for CML.
34
UI - 11879324
AU - Parmar KK; King RS
TI -
Imatinib mesylate: a new pill for chronic myelogenous leukemia.
SO - Cancer Pract 2001 Sep-Oct;9(5):263-5
AD - Department of Pharmacy Services, Temple University Hospital,
Philadelphia, Pennsylvania, USA.
35
UI - 11905088
AU - Nadav L; Eldor A
TI -
[Signal transduction inhibitor--STI571--a new treatment for chronic
myeloid leukemia (CML), which opens a new targeted approach to cancer
therapy]
SO - Harefuah 2002 Feb;141(2):158-62, 222
AD - Institute of Hematology, Sourasky Medical Center, Tel-Aviv, Israel.
Chronic myeloid leukemia (CML), in most of the cases, is the molecular
consequence of the t(9,22) translocation, resulting in the Philadelphia
(Ph) chromosome and the creation of the fusion gene BCR-ABL. The fusion
gene is translated to the protooncogen BCR-ABL, a constitutively
activated tyrosine kinase that is linked to the malignant
transformation. Thus, this tyrosine kinase became an attractive target
for drug design. The development of the novel investigational drug STI
571 is based on its potent and selective ability to inhibit this fusion
tyrosine kinase. In preclinical studies, STI 571 selectively inhibited
the growth of CML cells that carry the Ph chromosome. In this review we
discuss the drug development and design, its mechanism of action, the
preclinical studies and the results of phase I and II clinical trials.
36
UI - 11895760
AU - Wadhwa J; Szydlo RM; Apperley JF; Chase A; Bua M; Marin D; Olavarria E;
TI -
Kanfer E; Goldman JM
Factors affecting duration of survival after onset of blastic
transformation of chronic myeloid leukemia.
SO - Blood 2002 Apr 1;99(7):2304-9
AD - Department of Haematology, Hammersmith Hospital and Faculty of Medicine,
Imperial College at Hammersmith Campus, Du Cane Road, London W12 0NN,
United Kingdom.
We analyzed factors having an impact on response to treatment and
survival in 78 consecutive patients with chronic myeloid leukemia (CML)
in blastic transformation (BT) referred to the Hammersmith Hospital from
least 30% blasts in blood or marrow or extramedullary blastic deposits.
Immunophenotyping of blasts showed 57 myeloid, 19 lymphoid, and 2
biphenotypic. The median age of the patients was 39.1 years (range,
11.3-73.4 years), with 55 males and 23 females. The median survival for
all patients after onset of BT was 8.2 months (95% CI, 6.4-10). Patients
in lymphoid BT survived longer than those in myeloid BT (median, 11.2
months versus 6.9 months, P =.052). Initial treatment varied; 41
patients received cytotoxic drugs, 8 underwent allogeneic or autologous
transplantation procedures, 21 received STI571 (imatinib mesylate,
Gleevec), 1 received radiotherapy, and 7 received no therapy. Of the 25
(32%) patients who achieved a "second chronic phase" with first therapy,
6 of 21 (29%) were treated with STI571 and 19 of 50 (38%) were treated
with chemotherapy, transplantation, or radiotherapy. Patients who
achieved a second chronic phase survived longer than those who did not
(median time from onset of BT 12.0 months versus 6.3 months, P =.0004).
In multivariate analysis the finding of more than 50% blast cells in the
blood and the presence of cytogenetic progression were independent
adverse prognostic variables for survival. We conclude that survival
after onset of BT has improved in recent years but is still
unsatisfactory. We speculate that the combined use of STI571 with
cytotoxic drugs may offer additional benefit.
37
UI - 11943347
AU - Gumus G; Sunguroglu A; Tukun A; Sayin DB; Bokesoy I
TI -
Common fragile sites associated with the breakpoints of chromosomal
aberrations in hematologic neoplasms.
SO - Cancer Genet Cytogenet 2002 Mar;133(2):168-71
AD - Ankara University, Faculty of Medicine, Medical Biology Department,
Ankara, Turkey. guvemg@yahoo.com
Fragile sites are specific regions of chromosomes prone to breakage when
cells are cultured under specific conditions. These sites are divided
into two classes: common and rare. Common fragile sites are expressed in
all individuals at different frequencies, whereas rare ones are found
only in certain individuals. Common and rare fragile sites have been
shown to display a number of characteristics of instability being
preferential sites for chromosomal deletions, duplications, and
rearrangements. Moreover, a majority of mapped oncogenes are located at
or near these fragile sites. These observations have led to the
suggestion that both classes of fragile sites may play a significant
role in chromosomal rearrangements involved in oncogene activation or
tumo
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