National Cancer Institute®
Last Modified: April 1, 2002
UI - 11818666
AU - Douer D
TI - Advances in the treatment of relapsed acute promyelocytic leukemia.
SO - Acta Haematol 2002;107(1):1-17
AD - Division of Hematology, Keck School of Medicine, USC/Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. firstname.lastname@example.org
The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Multiple studies have established that combination of ATRA and chemotherapy in newly diagnosed patients has increased the cure rate to 70% from 35% in patients treated with chemotherapy alone. However, still about 30% of the patients relapse and are often resistant to ATRA retreatment. Consequently, a number of novel agents that include several differentiation agents and monoclonal antibodies have been studied to provide improved outcomes for patients with APL who have relapsed. In particular, arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. The unique mechanisms of action by which arsenic trioxide exerts its effects are complementary to those of ATRA, potentially allowing for combination therapies with additive or even synergistic results. Within this context autologous or allogeneic bone marrow transplantations are also considered in second or subsequent relapse, especially after arsenic trioxide-induced complete remission in relapsing patients. Furthermore, molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse of APL before clinical relapse, ultimately improving chances of prolonged remission. Copyright 2002 S. Karger AG, Basel
UI - 11868364
AU - Yata K; Yamada O; Iwato K; Kyo T; Otsuki T; Nakanishi H; Suetsugu Y;
TI - Mikami M; Wada H; Yawata Y; Sugihara T [Acute myelogenous leukemia associated with severe esophageal stricture after chemotherapy]
SO - Rinsho Ketsueki 2002 Jan;43(1):41-3
AD - Division of Hematology, Department of Medicine, Kawasaki Medical School.
A 41-year-old woman with relapsed acute myelogenous leukemia was treated twice with idarubicin hydrochloride and cytarabine. She developed a 6-cm-long stricture in the lower esophagus 12 days after re-induction therapy. Although she had preceding candida infection, it is suspected that her stricture was caused by mucosal damage due to chemotherapeutic agents. This case suggests that the possibility of esophageal stricture should be considered in patients with swallowing disturbance after intensive chemotherapy.
UI - 11781652
AU - Tack DK; Letendre L; Kamath PS; Tefferi A
TI - Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia.
SO - Bone Marrow Transplant 2001 Nov;28(9):895-7
AD - Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Mylotarg (gemtuzumab zogamicin) is a conjugated monoclonal antibody that has recently become available for use in patients with relapsing or refractory acute myeloid leukemia. Reversible hepatotoxicity is common after administration. We describe the first report of hepatic veno-occlusive disease (HVOD) developing after Mylotarg infusion in a patient who underwent hematopoietic stem cell transplantation 8 months earlier. Certain antineoplastic agents have been implicated as a cause of HVOD, but the disease is most commonly seen within 30 days after hematopoietic stem cell transplantation. The possible association between Mylotarg infusion and HVOD is discussed.
UI - 11842488
AU - White C
TI - Painful lesions in a pancytopenic patient.
SO - Clin J Oncol Nurs 2002 Jan-Feb;6(1):47-9, 51
AD - Loyola University Medical Center, Foster McGaw Hospital, in Maywood, IL, USA. email@example.com
UI - 11921269
AU - Rowley JD; Olney HJ
TI - International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: overview report.
SO - Genes Chromosomes Cancer 2002 Apr;33(4):331-45
AD - Department of Medicine, University of Chicago, Chicago, Illinois, USA. firstname.lastname@example.org
UI - 10578153
AU - Burt RK; Drobyski WR; Traynor AE; Link CJ Jr
TI - Herpes simplex thymidine kinase (HStk) transgenic donor lymphocytes.
SO - Bone Marrow Transplant 1999 Nov;24(10):1043-51
AD - Northwestern University School of Medicine, Robert H Lurie Cancer Center, Chicago, IL, USA.
Patients with recurrent leukemia after an allogeneic hematopoietic stem cell transplant may be treated with donor lymphocyte infusions (DLI). The transfusion of lymphocytes from the original hematopoietic stem cell donor induces remission in approximately one third of relapsed AML cases and 80% of relapsed CML. DLI may be complicated by delayed and sometimes lethal graft-versus-host disease (GVHD). In an attempt to avoid this complication, several centers have initiated DLI trials in which the infused lymphocytes carry a suicide gene, herpes simplex thymidine kinase (HStk), which confers sensitivity to ganciclovir (GCV). In the event of severe GVHD, administration of GCV should terminate or ameliorate GVHD.
UI - 11410481
AU - Bross PF; Beitz J; Chen G; Chen XH; Duffy E; Kieffer L; Roy S; Sridhara
TI - R; Rahman A; Williams G; Pazdur R Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.
SO - Clin Cancer Res 2001 Jun;7(6):1490-6
AD - Division of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA. email@example.com
PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration. EXPERIMENTAL DESIGN: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and its activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML. RESULTS: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells. The Phase 2 dose was 9 mg/m(2) infused i.v. over 4 h, repeated on day 14. A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization. The complete response (CR) rate with full recovery of hematopoiesis was 16%. A subset of patients [CRs with incomplete platelet recovery (CRps)] was identified with blast clearance and neutrophil recovery but incomplete platelet recovery. The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small. The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.
UI - 11852722
AU - Simpson JK; Rosenzweig MQ
TI - Treatment considerations for the elderly person with cancer.
SO - AACN Clin Issues 2002 Feb;13(1):43-60
AD - University of Pittsburgh, Graduate School of Public Health, Women's Health Office, 516 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA. firstname.lastname@example.org
In an aging population, the number of patients with cancer continues to rise. Little research has focused on the treatment of cancer in the elderly. Therefore, the treatment for various cancers differs across the healthcare system. A uniform approach in assessing the elderly person with cancer is lacking. This article describes two case studies in the elderly population, focusing on two common cancers: acute myelogenous leukemia and breast cancer. Common side effects of treatment and determinants of treatment options are discussed. It is important that the elderly receive appropriate screening, early detection, treatment, and management of comorbidities.
UI - 11898239
AU - Treish IM
TI - Targeting leukemia cells with gemtuzumab ozogamicin.
SO - Cancer Pract 2000 Sep-Oct;8(5):254-7
AD - Department of Pharmacy, University of North Carolina Hospitals, Chapel Hill, North Carolina, USA.
UI - 11823950
AU - Reinhardt D; Thiele C; Creutzig U; AML-BFM-Studiengruppe
TI - [Neuropsychological sequelae in children with AML treated with or without prophylactic CNS-irradiation]
SO - Klin Padiatr 2002 Jan-Feb;214(1):22-9
AD - Padiatrische Hamatologie/Onkologie, Westfalischen-Wilhelms Universitat, Munster. email@example.com
BACKGROUND: In study AML-BFM 87 the relapse rate was lower in patients receiving cranial irradiation (CRT). However, CRT has always been associated with adverse cognitive side effects. Therefore, the impact of CRT on neuropsychological function in children with AML was retrospectively evaluated. PATIENTS: We tested 53 children (30 boys, 23 girls) treated according to the AML-BFM-87 protocol (median age at diagnosis: 8.5 years, range 0.3 - 17.5; median time since diagnosis: 5.7 yrs, 3.8 - 10.7 yrs). To avoid any bias from additional therapy elements, patients with relapse or initial CNS involvement and transplanted patients were excluded (n=32). Our cohort was representative of the total group of 104 long term survivors of study AML-BFM 87. CNS prophylaxis consisted of ARA-C i.th., high dose ARA-C i. v. and either no CRT (n=15) or CRT (n=38) at a dose of 12 - 18 Gy depending on age. METHODS: Neuropsychological function was evaluated by psychological tests of attention and concentration (test d2 by Brickenkamp) and an intelligence test (Progressive Matrices by Raven). In addition, patients and their parents were interviewed about the occurrence of learning problems, subjective deficits in concentration and physical impairment. RESULTS: In the total group, no significant differences were seen between irradiated and non-irradiated patients regarding the psychological tests. However, the irradiated patients scored below the non-irradiated control group in test "d2" (concentration: 41st vs. 59th percentile). In the interview, irradiated patients tended to report more learning problems (lp) (10/36 vs. 1/14; p=0.15) and subjective deficits in concentration (con). In irradiated girls (con: 6/15 vs. 0/8; p=0.06; lp: 5/15 vs. 0/8; p=0.12) and younger patients (0 - 5 years at diagnosis; con: 7/12 vs. 2/9; p=0.18; lp 3/10 vs. 1/9; p=0.18) this trend was even more pronounced. CONCLUSION: Children with AML and CRT had no significant intellectual impairment in standardized tests when compared to non-irradiated patients. However, more irradiated patients reported learning problems and subjective concentration deficits.
UI - 11836177
AU - Martinez-Chamorro C; Martinez E; Gil-Fernandez JJ; Alonso A; Escudero A;
TI - Fernandez-Ranada JM ATRA-induced myositis in induction therapy of acute promyelocytic leukemia.
SO - Haematologica 2002 Feb;87(2):ECR08
AD - C/ General Oraa, 3-1, 28006- Madrid SPAIN. firstname.lastname@example.org
UI - 11836180
AU - Spedini P
TI - Retinoic acid syndrome: a case of massive lung consolidation.
SO - Haematologica 2002 Feb;87(2):EIM06
AD - Divisione di Medicina II, Sezione di Ematologia, Istituti Ospitalieri di Cremona, Italy.
UI - 11836189
AU - Breccia M; Cimino G; Alimena G; De Carolis S; Lo Coco F; Mandelli F
TI - AIDA treatment for high-risk acute promyelocytic leukemia in a pregnant woman at 21 weeks of gestation.
SO - Haematologica 2002 Feb;87(2):ELT12
AD - Dept. of Human Biotechnology and Hematology of the University La Sapienza of Roma, Via Benevento 6, 00161 Roma, Italy. email@example.com
UI - 11907794
AU - Astudillo L; Loche F; Reynish W; Rigal-Huguet F; Lamant L; Pris J
TI - Sweet's syndrome associated with retinoic acid syndrome in a patient with promyelocytic leukemia.
SO - Ann Hematol 2002 Feb;81(2):111-4
AD - Department of Haematology, University Hospital, Toulouse, France. firstname.lastname@example.org
We report a case of Sweet's syndrome associated with retinoic acid syndrome in a patient with acute promyelocytic leukemia treated with all- trans retinoic acid (ATRA). Sweet's syndrome appeared on day 6 of ATRA therapy for promyelocytic leukemia. It was associated with a mild retinoic acid syndrome, an inflammatory syndrome occurring in 25% of patients treated with ATRA and characterized by features of capillary leakage with systemic inflammatory signs. The ATRA therapy was discontinued for 11 days and treatment with corticosteroids improved the systemic and cutaneous signs. Only 11 cases of Sweet's syndrome associated with ATRA have been previously reported in the literature, involving only the skin in eight cases, the skin and muscles in two cases, and the lung, kidney, fascia, and muscles in one case. Sweet's syndrome was followed by retinoic acid syndrome in one of these cases. The previously reported cases are reviewed, and the mechanisms of Sweet's and retinoic acid syndromes and the link between them are discussed.
UI - 11896112
AU - Furman WL; Stewart CF; Kirstein M; Kepner JL; Bernstein ML; Kung F;
TI - Vietti TJ; Steuber CP; Becton DL; Baruchel S; Pratt C Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study.
SO - J Clin Oncol 2002 Mar 15;20(6):1617-24
AD - Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. email@example.com
PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.
UI - 11930660
AU - Chen Z; Wang Y; Wang W; Gong J; Xue Y
TI - All-trans retinoic acid as a single agent induces complete remission in a patient with acute leukemia of M2a subtype.
SO - Chin Med J (Engl) 2002 Jan;115(1):58-61
AD - First Affiliated Hospital, Suzhou University, Jiangsu Institute of Hematology, Suzhou 215006, China. firstname.lastname@example.org
OBJECTIVE: To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone. METHODS: A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60 mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course. RESULTS: The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RAR alpha fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. CONCLUSION: A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RAR alpha fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.
UI - 11267978
AU - Hsu CP; Yang CC; Yang SD
TI - Suppression of proline-directed protein kinase F(A) systemically inhibits the growth of human acute leukemia cells.
SO - Int J Cancer 2001 Mar 1;91(5):650-53
AD - Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
Initial studies revealed that proline-directed protein kinase F(A) (PDPK F(A)) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK F(A) in cancer remains to be established. In this report, we explore the potential role of PDPK F(A) in leukemia cell growth by investigating the effects of partial inhibition of this kinase on human acute promyelocytic leukemia (HL-60) and acute lymphoblastic leukemia (Jurkat) cells. Cloning of PDPK F(A) cDNA and its recombinant antisense expression vector and antibody were successfully developed. Several stable antisense clones of HL-60 and Jurkat cells were subcloned, which expressed a low level of PDPK F(A) when compared with the control-transfected clone in immunoblot analysis. Moreover, these antisense clones potently inhibited cell growth, clonogenic growth in soft agar and serum-independent growth. The results taken together demonstrate that suppression of PDPK F(A) is able to interfere with the growth of HL-60 and Jurkat cells, suggesting an essential role of this PDPK in human acute leukemia cell growth. Copyright 2001 Wiley-Liss, Inc.
UI - 11371621
AU - Pendino F; Flexor M; Delhommeau F; Buet D; Lanotte M; Segal-Bendirdjian
TI - E Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation.
SO - Proc Natl Acad Sci U S A 2001 Jun 5;98(12):6662-7
AD - Institut National de la Sante et de la Recherche Medicale U496, Centre G. Hayem, Hopital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France.
Human telomerase, a cellular reverse transcriptase (hTERT), is a nuclear ribonucleoprotein enzyme complex that catalyzes the synthesis and extension of telomeric DNA. This enzyme is specifically activated in most malignant tumors but is usually inactive in normal somatic cells, suggesting that telomerase plays an important role in cellular immortalization and tumorigenesis. Terminal maturation of tumor cells has been associated with the repression of telomerase activity. Using maturation-sensitive and -resistant NB4 cell lines, we analyzed the pattern of telomerase expression during the therapeutic treatment of acute promyelocytic leukemia (APL) by retinoids. Two pathways leading to the down-regulation of hTERT and telomerase activity were identified. The first pathway results in a rapid down-regulation of telomerase that is associated with retinoic acid receptor (RAR)-dependent maturation of NB4 cells. Furthermore, during NB4 cell maturation, obtained independently of RAR by retinoic X receptor (RXR)-specific agonists (rexinoids), no change in telomerase activity was observed, suggesting that hTERT regulation requires a specific signaling and occurs autonomously. A second pathway of hTERT regulation, identified in the RAR-responsive, maturation-resistant NB4-R1 cell line, results in a down-regulation of telomerase that develops slowly during two weeks of all-trans retinoic acid (ATRA) treatment. This pathway leads to telomere shortening, growth arrest, and cell death, all events that are overcome by ectopic expression of hTERT. These findings demonstrate a clear and full dissociation between the process of tumor cell maturation and the regulation of hTERT mRNA expression and telomerase activity by retinoids. We propose telomerase expression as an efficient and selective target of retinoids in the therapy of tumors.
UI - 11911247
AU - Faderl S; Estrov Z; Kantarjian H M; Harris D; Van Q; Fokt I; Przewloka
TI - T; Godlewski C; Woynarowski J M; 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.
UI - 11902306
AU - Huang F S; Zwerdling T; Stern L E; Ballard E T; Warner B W
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.
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.
UI - 11843281
AU - Mikoshiba M; Ohashi K; Takei N; Okuyama Y; Maeda Y; Hiruma K; Akiyama H;
TI - Fukuhara O; Takeshita A; Sakamaki H Successful unrelated bone marrow transplantation after arsenic trioxide treatment in a patient with relapsed acute promyelocytic leukemia.
SO - Int J Hematol 2002 Jan;75(1):104-6
UI - 11823363
AU - Greaves M
TI - Childhood leukaemia.
SO - BMJ 2002 Feb 2;324(7332):283-7
AD - Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB. email@example.com
UI - 11830487
AU - Zhou DC; Kim SH; Ding W; Schultz C; Warrell RP Jr; Gallagher RE
TI - Frequent mutations in the ligand-binding domain of PML-RARalpha after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo.
SO - Blood 2002 Feb 15;99(4):1356-63
AD - Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY 10467, USA.
This study identified missense mutations in the ligand binding domain of the oncoprotein PML-RARalpha in 5 of 8 patients with acute promyelocytic leukemia (APL) with 2 or more relapses and 2 or more previous courses of all-trans retinoic acid (RA)-containing therapy. Four mutations were novel (Lys207Asn, Gly289Arg, Arg294Trp, and Pro407Ser), whereas one had been previously identified (Arg272Gln; normal RARalpha1 codon assignment). Five patients were treated with repeat RA plus phenylbutyrate (PB), a histone deacetylase inhibitor, and one patient experienced a prolonged clinical remission. Of the 5 RA + PB-treated patients, 4 had PML-RARalpha mutations. The Gly289Arg mutation in the clinical responder produced the most defective PML-RARalpha function in the presence of RA with or without sodium butyrate (NaB) or trichostatin A. Relapse APL cells from this patient failed to differentiate in response to RA but partially differentiated in response to NaB alone, which was augmented by RA. In contrast, NaB alone had no differentiation effect on APL cells from another mutant case (Pro407Ser) but enhanced differentiation induced by RA. These results indicate that PML-RARalpha mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RARalpha was not correlated with clinical response to RA + PB treatment, and suggest that the response to RA + PB therapy in one patient was related to the ability of PB to circumvent the blocked RA-regulated gene response pathway.
UI - 11783227
AU - Hu X; Ma L; Hu N
TI - [Ailing No. I in treating 62 cases of acute promyelocytic leukemia]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 1999 Aug;19(8):473-6
AD - Xiyuan Hospital, China Academy of TCM, Beijing, China.
OBJECTIVE: To obtain further knowledge on the effect, mechanism and toxic side-effect of Ailing No. I (AL), a preparation of As2O3, in treating acute promyelocytic leukemia (APL). METHODS: AL was used in induction and consolidation treatment of 62 cases of APL, the effect of treatment and the changes of clinical symptoms, peripheral blood and bone marrow pictures, T-lymphocyte subset, and immunofunctions of patients after treatment were observed. RESULTS: Twenty-seven cases out of the 31 patients who received induction treatment got complete remission (CR), the CR rate being 87.1%. Of the 31 cases who received consolidation treatment, the longest remission period was 37 months, and 7 cases relapsed within one month to 2 years. Peripheral white blood cell count raised after one week but lowered after 4 weeks of induction treatment, but in receiving consolidation treatment, it started to lower after one week and raised after 4 weeks of treatment. No obvious change on hemoglobin level was observed. Platelet count significantly increased after treatment. The treatment showed no obvious inhibition on bone marrow. The T-lymphocyte subsets and immunoglobulin level were changed insignificantly after treatment. Various side-effects were shown clinically, particularly those digestive tract involved symptoms were prominent, and liver damage was shown in a certain degree. CONCLUSION: AL has good and protracted effect in treating APL with high CR rate, the mechanism may be related with its cytotoxicity and action of differentiation induction.
UI - 11899326
AU - Sorokin P
TI - Mylotarg approved for patients with CD33+ acute myeloid leukemia.
SO - Clin J Oncol Nurs 2000 Nov-Dec;4(6):279-80
Acute myeloid leukemia (AML) is the most common adult leukemia and has historically been treated with intensive multiagent chemotherapy. In May 2000, the U.S. Food and Drug Administration approved a new agent, gemtuzumab ozogamicin (Mylotarg) to treat patients who are 60 years and older in first relapse with CD33+ AML and not considered candidates for chemotherapy. Gemtuzumab is an antibody-targeted agent that binds specifically to the CD33 antigen that is found on the surface of more than 80% of patients with AML. The agent is administered via i.v. over two hours, and premedication with acetaminophen and diphenhydramine is recommended. Side effects include fever, chills, neutropenia and thrombocytopenia, and asymptomatic hypotension. Clinical remissions have been observed with gemtuzumab, and additional trials with this new agent currently are being conducted.
UI - 11951090
AU - Aquino VM
TI - Acute myelogenous leukemia.
SO - Curr Probl Pediatr Adolesc Health Care 2002 Feb;32(2):50-8
AD - Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
UI - 11953850
AU - Perrillat F; Clavel J; Auclerc MF; Baruchel A; Leverger G; Nelken B;
TI - Philippe N; Schaison G; Sommelet D; Vilmer E; Hemon D Day-care, early common infections and childhood acute leukaemia: a multicentre French case-control study.
SO - Br J Cancer 2002 Apr 8;86(7):1064-9
AD - Institut National de la Sante et de la Recherche Medicale, Inserm U170, 16 avenue Paul Vaillant Couturier, 94807 Villejuif, France.
We conducted a case-control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4-1.0)), repeated early common infections (> or = 4 per year before age two, odds ratio=0.6 (0.4-1.0)), surgical procedures for ear-nose-throat infections before age two (odds ratio=0.5 (0.2-1.0)) and prolonged breast-feeding (> or = 6 months, odds ratio=0.5 (0.2-1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5-2.3) and odds ratio=0.8 (0.5-1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1-0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia.
UI - 11879303
AU - Lam MS; Ignoffo RJ
TI - Arsenic trioxide for the treatment of acute promyelocytic leukemia.
SO - Cancer Pract 2001 May-Jun;9(3):155-7
AD - School of Clinical Pharmacy, University of California, San Francisco, California, USA.
UI - 11879277
AU - Alfiere M; Syombathy V
TI - The challenge of providing culturally competent cancer care.
SO - Cancer Pract 2001 Mar-Apr;9(2):62-3
AD - Medical Oncology Inpatient Unit, Yale New Haven Hospital, New Haven, Connecticut, USA.
UI - 11882366
AU - Sora F; Antinori A; Piccirillo N; De Luca A; Chiusolo P; Cingolani A;
TI - Laurenti L; Rutella S; Ortona L; Leone G; Sica S Highly active antiretroviral therapy and allogeneic CD34(+) peripheral blood progenitor cells transplantation in an HIV/HCV coinfected patient with acute myeloid leukemia.
SO - Exp Hematol 2002 Mar;30(3):279-84
AD - Istituto di Ematologia, Universita Cattolica Sacro Cuore, Rome, Italy.
OBJECTIVE: To evaluate the safety, feasibility, and efficacy of allogeneic stem cell transplantation (SCT) for acute myelogenous leukemia (AML) in a young female coinfected by HIV and HCV undergoing highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: A 33-year-old female HIV(+), HCV(+) in complete remission after standard chemotherapy was submitted to CD34(+) selected allogeneic transplantation from her HLA-identical HIV(-) brother after myeloablative regimen. HAART was started before transplantation, achieving a reduction of HIV load to undetectable levels. GVHD prophylaxis was carried out with cyclosporine A alone. RESULTS: The patient achieved prompt and durable engraftment with acute GVHD grade II easily managed with steroids; CMV prophylaxis was prolonged, no clinically relevant infectious complications developed early after transplantation and during follow-up. HIV viremia was controlled by HAART although medication adherence was reduced early after transplantation and required drug adjustment. There was a gradual recovery of immune cells with normal CD4-cell count 39 months after engraftment, a significantly higher level than before transplantation. At 39 months post-transplantation follow-up the patient is alive and in continuous complete remission with undetectable levels of plasma HIV RNA on HAART. CONCLUSION: The introduction of HAART has recently changed the paradigm of AIDS, allowing the control of HIV replication, the reduction of opportunistic infections, and the overall improvement of survival. One may therefore reconsider the current exclusion of patients with AIDS and a concomitant lethal malignancy from programs of high-dose chemotherapy and stem cell transplantation, as suggested by this report.
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