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NCI CANCERLIT® Search: Therapy of Acute Myeloid Leukemia - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Second allogeneic hematopoietic stem cell transplantation for leukemia relapse after first allogeneic transplantation: outcome of 16 patients
- Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.
- Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia.
- WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity.
- Autologous transplantation in acute myeloid leukemia: peripheral blood stem cell harvest after mobilization in steady state by granulocyte
- Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed
- Uncertain role of increased intensity chemotherapy with high-dose cytarabine in acute promyelocytic leukemia.
- Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report.
- Quantitative detection of serum adenovirus in a transplant recipient.
- [Not an easy life]
- Mydriasis after the treatment of vindesine in a patient with acute promyelocytic leukemia.
- In vitro activity of glufosfamide in childhood acute leukemia.
- A minor's refusal of treatment.
- Interleukin-2: clinical applications.
- A case of pancreatitis associated with all-trans-retinoic acid therapy in acute promyelocytic leukemia.
Table of Contents
1
UI - 11999364
AU - Tomonari A; Iseki T; Ooi J; Nagayama H; Sato H; Takahashi T; Ito K;
TI -
Nagamura F; Uchimaru K; Takahashi S; Shirafuji N; Tojo A; Tani K; Asano
S
Second allogeneic hematopoietic stem cell transplantation for leukemia
relapse after first allogeneic transplantation: outcome of 16 patients
in a single institution.
SO - Int J Hematol 2002 Apr;75(3):318-23
AD - Department of Hematology/Oncology, The Institute of Medical Science, The
University of Tokyo, Japan. atomonar@ims.u-tokyo.ac.jp
Sixteen patients who underwent a second allogeneic hematopoietic stem
cell transplantation (HSCT2) for leukemia relapse after the first
allogeneic transplantation (HSCT1) were studied. The patients included 7
patients with acute myelogenous leukemia, 8 with acute lymphoblastic
leukemia, and 1 with chronic myelogenous leukemia. The median patient
age at HSCT2 was 22 years (range, 12 to 44 years). The median interval
between HSCT1 and HSCT2 was 19 months (range, 2 to 46 months). At HSCT2,
7 patients were in complete remission (CR), 7 had relapsed, and 2 had
bone marrow aplasia. In 14 patients, donors for HSCT2 were the same as
those for HSCT1. Two donors were replaced, 1 for another HLA-matched
sibling and 1 for an unrelated cord blood donor. Four patients (25%)
died within 100 days after HSCT2 from veno-occlusive disease, sepsis,
interstitial pneumonitis, or chronic graft-versus-host disease (GVHD),
without leukemia relapse. Seven patients (44%) developed leukemia
relapse and died between 4 and 20 months after HSCT2. Five patients
(31%) survived beyond 4 years. One patient died from chronic GVHD
without leukemia relapse 55 months after HSCT2. The 4 other patients
were alive between 79 and 134 months after HSCT2 (median follow-up, 106
months). Factors that favorably influenced survival were age younger
than 20 years and CR duration after HSCT1 longer than 12 months. HSCT2
is considered to be beneficial for select patients. Preparative
regimens, GVHD prophylaxis, and donor choice for HSCT2 need to be
studied to obtain a more successful outcome for HSCT2.
2
UI - 11999366
AU - Saito T; Shinagawa K; Takenaka K; Matsuo K; Yoshino T; Kiura K; Niiya K;
TI -
Harada M
Ocular manifestation of acute graft-versus-host disease after allogeneic
peripheral blood stem cell transplantation.
SO - Int J Hematol 2002 Apr;75(3):332-4
AD - Second Department of Internal Medicine, Okayama University Medical
School, Japan.
A 26-year-old woman with acute myeloid leukemia underwent allogeneic
peripheral blood stem cell transplantation from an HLA-identical
brother. Eighteen days after transplantation, the patient developed
grade II acute graft-versus-host disease (GVHD) and was treated with
corticosteroids. On day 38, the patient complained of eye pain and
lacrimation. A slitlamp examination revealed corneal ulcers and
pseudomembranous formation in both eyes. Histologic and
immunohistochemical examinations of the pseudomembrane disclosed an
infiltrate dominated by T cells. A cytogenetic study of the
pseudomembrane by fluorescence in situ hybridization identified a Y
chromosome in the infiltrated mononuclear cells. Surveillance cultures
from conjunctival swabs were negative. Thus, we diagnosed these ocular
manifestations as an ocular involvement of acute GVHD.
3
UI - 11902306
AU - Huang FS; Zwerdling T; Stern LE; Ballard ET; Warner BW
TI -
Renal cell carcinoma as a secondary malignancy after treatment of acute
promyelocytic leukemia.
SO - J Pediatr Hematol Oncol 2001 Dec;23(9):609-11
AD - Division of Hematology/Oncology, Children's Hospital Medical Center,
Cincinnati, Ohio 45229-3039, USA.
Numerous children have been treated successfully for cancer and are
surviving into adulthood. As this population has aged, an increasing
number of secondary malignancies has emerged. Renal cell carcinoma (RCC)
is a rare tumor in childhood and has not been documented previously to
occur after treatment of acute promyelocytic leukemia (APL). This report
describes the clinical course of APL treated in a child in whom RCC
subsequently developed during adolescence approximately 5 years after
therapy.
4
UI - 11911247
AU - Faderl S; Estrov Z; Kantarjian HM; Harris D; Van Q; Fokt I; Przewloka T;
TI -
Godlewski C; Woynarowski JM; Priebe W
WP744, a novel anthracycline with enhanced proapoptotic and antileukemic
activity.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3777-84
AD - The University of Texas M. D. Anderson Cancer Center, Houston 77030,
USA.
BACKGROUND: MDR1 or MRP1 drug resistance mechanisms seriously limit the
efficacy of anthracyclines such as doxorubicin, in the treatment of
acute myeloid leukemia (AML). Our studies indicated that reducing
basicity, increasing steric hindrance at C-4', and/or lipophilicity may
help circumvent P-glycoprotein (P-gp)-mediated anthracycline efflux and
thus increase drug retention in MDR-positive cells. From a series of
4'-substituted analogs, 4'-O-benzylated doxorubicin (WP744) was selected
for a comparison with the classic anthracycline doxorubicin for their
cytotoxic and pro-apoptotic properties. WP744 retains cytotoxic activity
against P-gp and MRP-positive cells. METHODS AND RESULTS: In three AML
cell lines (K562, KBM-3, and OCIM2) WP744 was markedly more potent (IC50
values of 0.18, <0.05, and <0.05 microg/ml, respectively) than
doxorubicin (IC50 values of >0.5, 0.07, and 0.09 microg/ml,
respectively). Likewise, WP744 inhibited the colony formation by AML-CFU
cells from fresh bone marrow of three AML patients more strongly than
doxorubicin. Cell growth inhibition by WP744 is accompanied by apoptosis
induction as shown by TUNEL assay in OCIM2 cells. WP744-induced
apoptosis appears to be mediated by caspase-3 as apoptotic changes were
abrogated in the presence of the caspase 3 inhibitor Z-DEVD-FMK.
Accordingly, caspase 3 activity was elevated in the lysates from
drug-treated cells. WP744 induced also cleavage of apoptotic marker
poly(ADP-ribose)polymerase (PARP). Finally, WP744 at 0.05 microM and
greater was a potent inducer of apoptosis (by quantitative DNA
fragmentation) in cultured human acute lymphoblastic leukemia (ALL) CEM
cells, compared to 0.5 microM doxorubicin needed for a similar effect.
CONCLUSION: The novel anthracycline WP744 was found to be an
antileukemic agent with proapoptotic activity superior to that of
doxorubicin.
5
UI - 11732869
AU - Voog E; Le QH; Philip I; Benetaib B; Michallet M; Fiere D; Thomas X
TI -
Autologous transplantation in acute myeloid leukemia: peripheral blood
stem cell harvest after mobilization in steady state by granulocyte
colony-stimulating factor alone.
SO - Ann Hematol 2001 Oct;80(10):584-91
AD - Service d'Hematologie, Hopital E. Herriot, Lyon, France.
In order to determine whether granulocyte colony-stimulating factor
(G-CSF) alone initiated during steady state was able to mobilize
peripheral blood stem cells (PBSC) in acute myeloid leukemia (AML) and
to assess predictive factors for engraftment after autologous PBSC
transplantation, we studied 49 successive adult AML patients for whom
1998. G-CSF was used as priming agent and was initiated at least 4 weeks
after the last day of chemotherapy, while neutrophil count was >0.5 x
10(9)/l and platelet count was >30 x 10(9)/l. A median of three
aphereses was performed resulting in a median collection of 14.8 x 10(8)
nucleated cells/kg containing 7.7 x 10(8) mononuclear cells/kg, 47.1 x
10(4) CFU-GM/kg, and 3.8 x 10(6) CD34+ cells/kg. A significant
correlation was observed between nucleated cell, mononuclear cell, and
CFU-GM yields, while no correlation was found with CD34+ cell yield.
Recruitment was not significantly different in patients with CD34+
leukemic cells at the time of initial diagnosis when compared to that of
those presenting with CD34- blastic cells. Thirty-three patients
actually underwent transplantation. Reasons for not autografting were
inadequate stem cell harvest (ten patients), early relapse (two
patients), prolonged neutropenia (one patient), organ failure (two
patients), or patient refusal (one patient). Median time to achieve a
neutrophil count greater than 0.5 x 10(9)/l and platelet count >50 x
10(9)/l untransfused was 13 and 36 days, respectively. A predictive
factor for a shorter period neutropenia and a shorter thrombopenia was a
higher count of harvested nucleated cells (p < 0.01 and p = 0.02,
respectively). A higher count of harvested cells was also a predictive
factor for less red cell and platelet transfusions (p=0.03 and p=0.02,
respectively). The number of CD34+ harvested PBSC was not predictive for
engraftment. We conclude that PBSC mobilization with G-CSF alone
initiated in steady state is a feasible, safe, and suitable procedure
for harvesting cells in sight of autologous transplantation in adult
acute myeloid leukemia.
6
UI - 10942230
AU - Lengfelder E; Reichert A; Schoch C; Haase D; Haferlach T; Loffler H;
TI -
Staib P; Heyll A; Seifarth W; Saussele S; Fonatsch C; Gassmann W; Ludwig
WD; Hochhaus A; Beelen D; Aul C; Sauerland MC; Heinecke A; Hehlmann R;
Wormann B; Hiddemann W; Buchner T
Double induction strategy including high dose cytarabine in combination
with all-trans retinoic acid: effects in patients with newly diagnosed
acute promyelocytic leukemia. German AML Cooperative Group.
SO - Leukemia 2000 Aug;14(8):1362-70
AD - III. Medizinische Klinik Mannheim, University of Heidelberg, Germany.
A prospective multicenter study was performed to investigate the
clinical and molecular results of intensified double induction therapy
including high-dose cytarabine (ara-C) in combination with ATRA in newly
diagnosed acute promyelocytic leukemia (APL), followed by consolidation
and 3 years maintenance therapy. Fifty-one patients, diagnosed and
age was 43 (16-60) years. The morphologic diagnosis was M3 in 40 (78%)
and M3v in 11 (22%) patients. In 15 (30%) patients the initial white
blood cell counts were > or =5 x 10(9)/l. The cytogenetic or molecular
proof of the translocation t(15;17) was a mandatory prerequisite for
eligibility. The diagnosis was confirmed by karyotyping in 46 and by
RT-PCR of the PML/RARalpha transcript in 45 cases. The rate of complete
hematological remission was 92% and the early death rate 8%. Monitoring
of minimal residual disease by RT-PCR of PML/RARalpha (sensitivity
10(-4)) showed negativity in 29 of 32 (91%) evaluable cases after
induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%)
during maintenance, after a median time of 2, 4 and of 18 months after
diagnosis, respectively. After a median follow-up of 27 months, the
estimated actuarial 2 years overall and event-free survival were both
88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The
high antileukemic efficacy of this treatment strategy is demonstrated by
a rapid and extensive reduction of the malignant clone and by a low
relapse rate. The results suggest that the intensity of the induction
chemotherapy combined with ATRA is one of the factors which may have a
critical influence on the outcome of APL. A randomized trial should
assess the value of an induction therapy including ATRA and high-dose
ara-C in comparison to standard-dose ara-C.
7
UI - 11753627
AU - Sanz MA; Martin G; Rayon C; Deben G; Tormo M; Diaz-Mediavilla J; Esteve
TI -
J; Gonzalez-San Miguel JD; Spanish PETHEMA Cooperative Group
Uncertain role of increased intensity chemotherapy with high-dose
cytarabine in acute promyelocytic leukemia.
SO - Leukemia 2001 Dec;15(12):1999-2002
8
UI - 11964275
AU - Lu DP; Qiu JY; Jiang B; Wang Q; Liu KY; Liu YR; Chen SS
TI -
Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic
leukemia: a pilot report.
SO - Blood 2002 May 1;99(9):3136-43
AD - Peking University Institute of Hematology and People's Hospital,
Beijing, China.
In the past 6 years, we treated 129 patients who had acute promyelocytic
leukemia (APL) with a new arsenic agent, oral tetra-arsenic
tetra-sulfide (As(4)S(4)). Nineteen of the patients had newly diagnosed
APL, 7 had first relapse, and 103 had hematologic complete remission
(HCR). HCR was achieved in all patients with newly diagnosed APL and in
all those with hematologic relapse. Of 16 patients with newly diagnosed
disease and available cytogenetic and molecular analyses, 14 had
cytogenetic and molecular complete remission (CR). Cytogenetic and
molecular CR was also obtained in 5 of the 7 patients with hematologic
relapse. In the HCR group, 35 of 44 patients positive for PML-RARalpha
at baseline became negative. In the newly diagnosed group, estimated
disease-free survival (DFS) rates for 1 and 3 years were 86.1% and
76.6%, respectively, with a median follow-up time of 13.5 months (range,
2-40 months). In the HCR group, DFS rates for 1 and 6 years were 96.7%
and 87.4%, respectively, with a median follow-up of 23 months (range,
2-71 months). Treatment with As(4)S(4) was well tolerated, with only
moderate side effects, including asymptomatic prolongation of corrected
QT interval, transient elevation in liver enzyme levels, rash, and mild
gastrointestinal discomfort; neither myelosuppression nor appreciable
long-term side effects occurred. Degeneration or apoptosis of APL
promyelocytes was observed during As(4)S(4) therapy. Pharmacokinetic
studies showed that the agent was absorbed rapidly. Most urinary arsenic
excretion occurred within the first 24 hours. Both blood and urinary
arsenic levels declined after discontinuation of As(4)S(4). Our results
show, for the first time, that As(4)S(4) treatment alone is highly
effective and safe in both remission induction and maintenance therapy
in patients with APL, regardless of disease stage.
9
UI - 12057576
AU - Teramura T; Naya M; Yoshihara T; Morimoto A; Imashuku S
TI -
Quantitative detection of serum adenovirus in a transplant recipient.
SO - Lancet 2002 Jun 1;359(9321):1945
10
UI - 11941776
AU - Kunz M
TI -
[Not an easy life]
SO - Krankenpfl Soins Infirm 2000 Apr;93(4):25
11
UI - 12040454
AU - Ashihara E; Shimazaki C; Takahashi R; Fuchida S; Ochiai N; Inaba T;
TI -
Nakagawa M
Mydriasis after the treatment of vindesine in a patient with acute
promyelocytic leukemia.
SO - Leukemia 2002 Jun;16(6):1200
12
UI - 12017297
AU - Styczynski J; Wysocki M; Kurylak A; Juraszewska E; Malinowska I;
TI -
Stanczak E; Ploszynska A; Stefaniak J; Mazur B; Szczepanski T; Ras M
In vitro activity of glufosfamide in childhood acute leukemia.
SO - Anticancer Res 2002 Jan-Feb;22(1A):247-50
AD - Katedra i Klinika Pediatrii, Hematologii i Onkologii, Bydgoszcz, Poland.
jan_styczynski@kki.net.pl
Glufosfamide is a new agent for cancer chemotherapy. The objective of
the study was the comparison of the in vitro drug resistance profile of
glufosfamide with other oxazaphosphorines in 106 samples of childhood
acute leukemia by means of the MTT assay. The following drugs were
tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide,
mafosfamide cyclohexylamine salt, prednisolone, vincristine,
L-asparaginase, daunorubicin and cytarabine. In the group of initial
Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity
values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and
mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In
comparison to initial ALL samples, the relative resistance for
glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9
(p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML)
samples, respectively, 31 (p<0.001) and 5 (p=0.001). All
oxazaphosphorines showed highly significant cross-resistance. In
conclusion, in vitro activity of glufosfamide is comparable to
ifosfamide. Glufosfamide shows high activity against lymphoblasts both
on diagnosis and on relapse, however it cannot circumvent resistance to
other oxazaphosphorines.
13
UI - 2115958
AU - Rhodes AM
TI -
A minor's refusal of treatment.
SO - MCN Am J Matern Child Nurs 1990 Jul-Aug;15(4):261
AD - Finance and University Services, University of Iowa, Iowa City.
14
UI - 12068383
AU - Atkins MB
TI -
Interleukin-2: clinical applications.
SO - Semin Oncol 2002 Jun;29(3 Suppl 7):12-7
AD - Cutaneous Oncology & Biologic Therapy Programs, Beth Israel Deaconess
Medical Center, Boston, MA 02215, USA.
Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the
treatment of metastatic melanoma, acute myelogenous leukemia, and
metastatic renal cell carcinoma. While high-dose IL-2 regimens have
shown clinical benefit in the treatment of melanoma and renal cell
carcinoma, serious dose-limiting toxicities have limited their clinical
use in a broader group of patients. Low-dose IL-2 therapy has produced
disappointing clinical response rates in melanoma. While the response
rates to low-dose IL-2 have been better in renal cell carcinoma, the
quality of these responses relative to those seen with high-dose IL-2
therapy remains a concern. The addition of IL-2 to chemotherapeutic
regimens (biochemotherapy) has been associated with overall response
rates of up to 60% in patients with metastatic melanoma, but this has
yet to be translated into a confirmed improvement in survival. It
remains to be determined whether further modifications of IL-2-based
regimens or the addition of newer agents to IL-2 will produce better
tumor response and survival. Copyright 2002, Elsevier Science (USA). All
rights reserved.
15
UI - 11920282
AU - Abou Chacra L; Ghosn M; Ghayad E; Honein K
TI -
A case of pancreatitis associated with all-trans-retinoic acid therapy
in acute promyelocytic leukemia.
SO - Hematol J 2001;2(6):406-7
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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