National Cancer Institute®
Last Modified: January 1, 2002
UI - 11452409
AU - Biagi E; Rovelli A; De Lorenzo P; Uderzo C
TI - Autologous hematopoietic stem cell transplantation (AHSCT) as consolidation therapy for childhood acute myelogenous leukemia in 1st complete remission.
SO - Pediatr Hematol Oncol 2001 Jul-Aug;18(5):359-62
UI - 11488854
AU - Hui CH; Bardy P; Hughes T; Horvath N; To LB
TI - Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases.
SO - Clin Lab Haematol 2001 Apr;23(2):135-8
AD - Clinical Haematology & Bone Marrow Transplant Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. firstname.lastname@example.org
Management options are often limited for patients with AML or high grade myelodysplasia (MDS) relapsing within a year of allogeneic transplantation. We report, in two such patients, the use of re-induction with FLAG-Ida chemotherapy, followed by the infusion of GCSF-mobilized blood stem cells from the same HLA-matched donor. Both patients achieved durable complete remissions with good quality of life and longer disease-free survival than after the first myeloablative allografts. This mini-allograft approach offers a practical, well-tolerated salvage and a potentially curative treatment for relapsed AML/high grade MDS patients failing a first conventional myeloablative allogeneic transplants.
UI - 11503549
AU - Koh LP; Goh YT; Teoh G; Tan P
TI - Treatment of acute promyelocytic leukaemia using a combination of all-trans retinoic acid and chemotherapy.
SO - Ann Acad Med Singapore 2001 Jul;30(4):401-8
AD - Department of Haematology, Singapore General Hospital, 1 Hospital Drive, Singapore 169608.
INTRODUCTION: The combination of all-trans retinoic acid (ATRA) with chemotherapy has improved the outcome of acute promyelocytic leukaemia (APL). Effective induction as well as maintenance therapy for APL can be achieved using this combination of anti-leukaemic agents. MATERIALS AND METHODS: Twenty-four consecutive patients with newly-diagnosed APL were treated with ATRA daily together with either daunorubicin or idarubicin. Therapy with ATRA was continued until complete remission (CR) was achieved; thereafter, patients were treated with 2 cycles of an anthracycline-based consolidation chemotherapy (either daunorubicin or idarubicin). Maintenance therapy was achieved using 5 alternating cycles of low-dose methotrexate (MTX) plus 6-mercaptopurine (6MP) followed by ATRA alone. RESULTS: Twenty-three out of 24 patients (96%) completed induction therapy and achieved haematological CR (HCR) as well as molecular remission (MR); however, 1 patient (5%) died from retinoic acid syndrome. Twenty-one out of 23 evaluable patients (91%) completed consolidation chemotherapy, and 2 patients (10%) died, 1 from neutropenic sepsis and the other from relapse following non-compliance to therapy. All 21 surviving patients in the present study received maintenance chemotherapy and are still in HCR and MR at a median follow-up of 23 months. The estimated actuarial 2-year overall survival (OS) and event-free survival (EFS) rates were both 84% +/- 9%. CONCLUSION: The combination of ATRA with an anthracycline is an effective remission-induction therapy for newly-diagnosed APL. Maintenance therapy using alternating cycles of MTX plus 6MP followed by ATRA alone is effective in maintaining CR and MR as well as prolonging the survival of patients with APL.
UI - 11571506
AU - Urbano-Ispizua A; Brunet S; Solano C; Moraleda JM; Rovira M; Zuazu J; de
TI - La Rubia J; Bargay J; Caballero D; Diez-Martin JL; Ojeda E; Perez de Oteiza JP; Ferra C; Espigado I; Alegre A; de La Serna J; Torres P; Riu C; Odriozola J; Rozman C; Sierra J; Garcia-Conde J; Montserrat E; Spanish Group of Allo-PBT Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation.
SO - Bone Marrow Transplant 2001 Aug;28(4):349-54
AD - Depatment of Hematology, Hospital Clinic, University of Barcelona, Spain.
An allogeneic transplantation of CD34(+)-selected cells from peripheral blood (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed in 50 adult patients with acute myeloid leukemia in first complete remission (AML CR1) (n = 29), myelodysplastic syndrome (MDS) (n = 4), or chronic myeloid leukemia in first chronic phase (CML CP1) (n = 17). Clinical results were compared to a concurrent group of 50 patients transplanted with unmodified peripheral blood progenitor cells (allo-PBT), matched for age, diagnosis, and disease stage. The median follow-up period was 29 months (range 1-69). The actuarial probability of developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26) for the allo-PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT group (P = 0.002). The actuarial probability of developing extensive chronic GVHD was 22% (95%CI: 8-36) for the allo-PBT/CD34(+) group and 47% (95%CI: 31-63) for the allo-PBT group (P = 0.02). Recipients of allo-PBT/CD34(+) had less toxicity associated with the transplant and better Karnofsky index at the last follow-up. For AML/MDS patients, the actuarial probability of disease-free survival (DFS) for recipients of allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI: 28-58) (P = 0.05), respectively. These data provide a rationale for a randomised trial of allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in early stage of the disease.
UI - 11571508
AU - Meloni G; Proia A; Capria S; Romano A; Trape G; Trisolini SM; Vignetti
TI - M; Mandelli F Obesity and autologous stem cell transplantation in acute myeloid leukemia.
SO - Bone Marrow Transplant 2001 Aug;28(4):365-7
AD - Department of Biotecnologie Cellulari ed Ematologia, University La Sapienza, Roma, Italy.
In the bone marrow transplant setting, several authors hypothesized that severely overweight patients are at increased risk of transplant-related toxicity, but different definitions of obesity, different body weight groupings and heterogeneous samples of patients were analyzed. To overcome these limitations, we retrospectively considered a homogeneous group of 54 patients (median age 36.5 years), with a diagnosis of de novo acute myeloid leukemia (AML), autografted in first complete remission (CR) with the Bu-Cy2 conditioning regimen, dosed on actual body weight. Patients were classified into three groups (obese, non-obese, underweight) using body mass index (BMI = kg/m(2)); for each group we analyzed transplant-related toxicity and mortality, overall survival and disease-free survival (OS/DFS). In spite of the relatively small number of patients, in our results high BMI appears a predictive factor for an increase of treatment-related toxicity and mortality. Moreover, 30 (55%) patients are currently alive in continuous CR, and after a median follow-up of 76.5 months (range 14-137) statistically significant differences in OS and DFS were detected between obese and non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests that obesity may represent an independent risk factor for autograft in AML and further investigations are warranted.
UI - 11571518
AU - Au WY; Lie AK; Lee CK; Ma SK; Wan TS; Shek TW; Liang R; Kwong YL
TI - Late onset post-transplantation lymphoproliferative disease of recipient origin following cytogenetic relapse and occult autologous haematopoietic regeneration after allogeneic bone marrow transplantation for acute myeloid leukaemia.
SO - Bone Marrow Transplant 2001 Aug;28(4):417-9
AD - Department of Medicine, Queen Mary Hospital, Hong Kong.
A post-transplantation lymphoproliferative disease (PTLD) of recipient origin was identified in one of 376 consecutive cases of allogeneic bone marrow transplantation (BMT). This occurred in a 36-year-old woman who received an allogeneic BMT for acute myeloid leukaemia in relapse. At 15 months after BMT, recipient haematopietic and leukaemic cells were found in the bone marrow, which disappeared on withdrawal of immunosuppression. However, severe graft-versus-host disease (GVHD) necessitated the continuation of immunosuppression, leading to the occurrence of PTLD in the liver and lung 12 months afterwards. Fluorescence in situ hybridisation showed that the neoplastic cells were of recipient origin. Although the PTLD also responded completely to withdrawal of immunosuppression, the patient finally died from the complications of GVHD. This case of late onset PTLD post-BMT showed features similar to those in solid organ transplantation, in that the tumour was of recipient origin and responded well to the withdrawal of immunosuppression. Of further interest is that recipient lymphoid regeneration had accompanied autologous haematopoietic regeneration and become a target for subsequent neoplastic transformation.
UI - 11568900
AU - Loeb DM; Bowers DC; Civin CI; Friedman AD
TI - Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia.
SO - Med Pediatr Oncol 2001 Oct;37(4):365-71
AD - Division of Pediatric Oncology, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.
BACKGROUND: Timed sequential chemotherapy and high-dose cytarabine (cytosine arabinoside, Ara-C; HDAC) are both effective treatments for acute myeloid leukemia (AML). We review our institutional experience with timed sequential induction chemotherapy consisting of daunorubicin/Ara-C/-thioguanine (DAT) or idarubicin/Ara-C/-thioguanine (IAT) followed on day 14 by HDAC regardless of the degree of marrow aplasia for children with newly diagnosed AML. PROCEDURE: Children presenting with newly diagnosed AML were treated with induction chemotherapy consisting of idarubicin (12 mg/m/day on days 1-3 or daunorubicin at 45 mg/m(2)/day for the first five patients), Ara-C (100 mg/m(2)/day by continuous infusion on days 1-7), and thioguanine (100 mg/m(2)/day on days 1-7). HDAC (1 g/m(2)/dose every 12 hr for 10 doses) was administered beginning on day 14, regardless of the results of bone marrow examination. RESULTS: Thirteen children received timed sequential HDAC. Only one child received HDAC later than Day 18. Eleven of the children achieved a complete remission. All patients experienced grade 4 hematologic toxicity, and all had fever as well. There were 11 children with documented infections. Ten had grade 3 or 4 GI toxicity. One patient died of sepsis. CONCLUSIONS: HDAC administered as a part of timed sequential therapy yields an excellent remission induction rate with manageable toxicity. Copyright 2001 Wiley-Liss, Inc.
UI - 11574763
AU - Hanel M; Friedrichsen K; Hanel A; Herbst R; Morgner A; Neser S;
TI - Nicklisch M; Teich M; Ehninger G; Fiedler F Mito-flag as salvage therapy for relapsed and refractory acute myeloid leukemia.
SO - Onkologie 2001 Aug;24(4):356-60
AD - Abteilung Hamatologie, Klinik fur Innere Medizin III/Kuchwald, Klinikum Chemnitz gGmbH, Chemnitz.
BACKGROUND: This study was performed to examine the feasibility and toxicity of the combination of mitoxantrone, fludarabine, cytarabine as bolus (B) or continuous infusion (CI) and granulocyte- colony stimulating factor (G-CSF) in patients with recurrent and refractory acute myeloid leukemia (AML). PATIENTS AND METHODS: 29 patients with relapsed (n =17) or refractory (n =12) AML were treated with the Mito-FLAG protocol consisting of mitoxantrone (7 mg/m(2), days 1/3/5), fludarabine (15mg/m(2), every 12 h, days 1-5), cytarabine (Ara-C) as bolus infusion (1000 mg/m(2) over 1 h, every 12 h, days 1-5) (n =15) or as continuous infusion (100-150 mg/m(2) over 24 h, days 1-5) (n =14), and G-CSF (5 mgr;g/ kg/day, day 0 until a neutrophile count of 0.5 x10(9)/l). RESULTS: 17 patients (59%) and 1 patient (3%) achieved complete remission (CR) and partial remission (PR), respectively; thus the overall response rate was 62%. Following Mito-FLAG, 5 patients with CR underwent high-dose therapy (HDT) with allogeneic (n = 2) or autologous (n = 3) stem cell transplantation (SCT).With a median follow-up of 28 (range 6-54) months, 4 transplanted patients are alive in CR (n = 2) or in relapse (n = 2). The median duration of event-free survival (EFS) and overall survival (OS) was 3.2 and 6.8 months, and probabilities of EFS and OS after 1 year were 14 and 34%, respectively. The 1-year rates for EFS and OS in this group were 18 and 53%, respectively. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was 20 and 23 days, respectively. Nonhematological side effects were moderate, predominantly reaching WHO grades 1-2. Neutropenic fever was seen in 85% of courses, with a median duration of 4 (1-38) days. Four patients (14%) suffered an early death because of aplasia (n = 2), pneumonia (n =1) or progressive AML (1 nonresponding patient). CONCLUSIONS: Our data suggest that the Mito-FLAG protocol is feasible and can be safely performed with both schedules of Ara-C. In this study the regimens have shown high efficacy and acceptable toxicity in patients with relapsed or refractory AML. We currently examine the importance of bolus versus continuous infusion of Ara-C as part of the Mito-FLAG regimen in a prospective randomized multicenter trial. Copyright 2001 S. Karger GmbH, Freiburg
UI - 11584711
AU - Wedding U; Hoffken K
TI - [Therapy of acute myeloid leukemia in the elderly patient]
SO - Z Gerontol Geriatr 2001 Aug;34(4):269-76
AD - Klinik fur Innere Medizin II Hamatologie, Onkologie, Endokrinologie, Stoffwechselerkrankungen Friedrich-Schiller-Universitat Erlanger Allee 101 07747 Jena, Germany. email@example.com
Incidence and mortality rates of acute myeloid leukemia (AML) increase exponentially with advancing age. AML diagnosed in elderly patients differs from that diagnosed in younger patients. But not only disease-specific differences are important. Treating elderly patients with AML age-associated differences in the patients general presentation, such as physiological changes in organ function, decreased ability to react to stress, dependence in activities of daily living, existence of other morbidities (co-morbidity), the need to take drugs for those diseases and the reduced life expectancy can force alterations in the disease management. Clinical trials for the treatment of AML have been excluding elderly patients for years. Even trials accepting elderly patients with AML did select the group of otherwise healthy elderly patients for participation in the trial. Thus the data for AML management in elderly patients do not reflect the whole group of elderly patients with AML. If the patient is treated with curative intention, therapy of choice is the so-called 3 + 7 protocol for induction of complete remission, followed by a consolidation therapy and in some cases by maintenance therapy. In some situations, especially in very old patients, a palliative intention to treatment is favored. There are no generally accepted criteria to measure treatment benefit in this setting nor established chemotherapy protocols for this situation. Further trials for elderly patients with AML have to offer treatment options for the whole group of patients and have to determine what treatment approach is the best for which individual patient.
UI - 11588026
AU - de Witte T; Suciu S; Verhoef G; Labar B; Archimbaud E; Aul C; Selleslag
TI - D; Ferrant A; Wijermans P; Mandelli F; Amadori S; Jehn U; Muus P; Boogaerts M; Zittoun R; Gratwohl A; Zwierzina H; Hagemeijer A; Willemze R Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS.
SO - Blood 2001 Oct 15;98(8):2326-31
AD - University Medical Center St Radboud, Nijmegen, The Netherlands. firstname.lastname@example.org
This study investigated the feasibility of allogeneic (alloSCT) and autologous stem cell transplantation (ASCT) as postconsolidation therapy for patients with myelodysplastic syndromes (MDSs) or acute myeloid leukemia after MDS. Patients with a histocompatible sibling were candidates for alloSCT and the remaining patients for ASCT. Remission-induction therapy consisted of 1 or 2 courses with idarubicin, cytarabine, and etoposide, followed by one intensive consolidation course with cytarabine and mitoxantrone. Initially, bone marrow cells were used for ASCT. Subsequently, mobilized blood stem cells were used in an attempt to shorten posttransplantation hypoplasia. With a median follow-up of 3.6 years the 184 evaluable patients showed a 4-year survival rate of 26% and a median survival of 13 months. The remission-induction chemotherapy induced complete remission (CR) in 100 patients (54%). The 4-year disease-free survival (DFS) rate was 29% and the median DFS was 12 months. Twenty-eight of 39 patients (72%) with a donor were allografted in CR-1, including 2 patients who underwent transplantation in CR-1 without a consolidation course. Thirty-six of 59 patients (61%) without a donor received ASCT in CR-1. The 4-year DFS rates in the group of patients with or without a donor were 31% and 27%, respectively. The 4-year survival rates from CR were 36% and 33%, respectively. This large prospective study shows the feasibility of both alloSCT and ASCT. This treatment approach leads to a relatively high remission rate, and the majority of patients in remission received the SCT in CR-1. The ongoing study investigates whether this approach is better than treatment with chemotherapy only.
UI - 11601256
AU - Shang X; Yin H; Lu A; Zhang L
TI - Application of recombinant human granulocyte colony stimulating factor in children with acute myeloid leukemia.
SO - Chin Med J (Engl) 1999 Jul;112(7):620-2
AD - Department of Pediatrics, Second Hospital, Beijing Medical University, Beijing 100044, China.
OBJECTIVE: To evaluate the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on accelerating neutrophil recovery and decrease fatal infections for childhood acute myeloid leukemia enrolled into our study and 15 were newly diagnosed. All were treated with high dose chemotherapy combined with rhG-CSF. RESULTS: Of 15 newly diagnosed patients, 13 achieved complete remission (CR) after one course of therapy and 2 achieved CR after two courses of therapy. For newly diagnosed patients, the durations of absolute neutrophil counts (ANC) < 0.5 x 10(9)/L were 5 days and 10 days in rhG-CSF group and control group respectively (P < 0.05). The incidences of infection of these two groups were 40% and 60% respectively (P < 0.05). As for patients who received intensive therapy, the durations of ANC < 0.5 x 10(9)/L were 5 days and 8 days in rhG-CSF group and control group, respectively (P < 0.05), and the incidences of infection were 25% and 44.4% respectively (P < 0.05). CONCLUSIONS: The application of rhG-CSF in children with AML after chemotherapy may hasten the hematopoietic recovery. The duration of neutropenia was shortened by 3-4 days, and the incidence of fatal infection was reduced. rhG-CSF does not stimulate AML growth in vivo.
UI - 11604554
AU - Tomita N; Kanamori H; Fujita H; Maruta A; Naitoh A; Nakamura S; Ota Y;
TI - Nozue N; Kihara M; Ishigatsubo Y Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.
SO - Anticancer Drugs 2001 Sep;12(8):677-80
AD - Department of Hematology , Fujieda Municipal General Hospital, Shizuoka, 426-8677, Japan. email@example.com
We report the first case of granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia (APL). Acute renal failure during treatment with ATRA has been previously reported as a part of an ATRA syndrome or a thrombotic complication of a hypercoagulable state. This case indicates an alternative mechanism of acute renal failure occurring during ATRA therapy.
UI - 11600603
AU - Specchia G; Lo Coco F; Vignetti M; Avvisati G; Fazi P; Albano F; Di
TI - Raimondo F; Martino B; Ferrara F; Selleri C; Liso V; Mandelli F Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell'Adulto.
SO - J Clin Oncol 2001 Oct 15;19(20):4023-8
AD - Department of Hematology, University of Bari, Bari, Italy. firstname.lastname@example.org
PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse. CONCLUSION: APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.
UI - 11602915
AU - Lengfelder E; Hehlmann R; Buchner T
TI - [Current therapeutic concept of acute promyelocytic leukemia]
SO - Dtsch Med Wochenschr 2001 Sep 28;126(39):1073-9
AD - III. Medizinische Universitatsklinik Mannheim, Universitat Heidelberg, Germany.
UI - 11673686
AU - Marie JP
TI - Drug resistance in hematologic malignancies.
SO - Curr Opin Oncol 2001 Nov;13(6):463-9
AD - Department of Hematology and Medical Oncology, University Paris 6, Paris, France. email@example.com
Drug resistance eventually occurs in most hematologic malignancies treated with chemotherapy. The mechanisms responsible for drug resistance include expression of transporters of xenobiotics of the adenosine triphosphate-binding cassette protein superfamily (P-glycoprotein, multidrug resistance associated proteins, breast cancer resistance protein), modifications of enzymes like deoxycytidine kinase, and defects in chemotherapy-induced apoptosis. The efforts to overcome this drug resistance have been focused, thus far, on modulation of P-glycoprotein. Several compounds were manufactured for this purpose, and phase III trials of PSC833, one of the most potent P-glycoprotein inhibitors, are completed. The emergence of modulators with several adenosine triphosphate-binding cassette protein targets, like GG120918 (inhibiting P-glycoprotein and breast cancer resistance protein) and VX710 (inhibiting P-glycoprotein and multidrug resistance associated protein 1), are of clinical interest in malignancies often expressing several efflux pumps simultaneously. Another approach is the use of "furtive" drugs like liposomal or nanoparticular anthracyclines.
UI - 11673694
AU - Sievers EL; Linenberger M
TI - Mylotarg: antibody-targeted chemotherapy comes of age.
SO - Curr Opin Oncol 2001 Nov;13(6):522-7
AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. firstname.lastname@example.org
Mylotarg (gemtuzumab ozogamicin, CMA-676; Wyeth-Ayerst Laboratories, Philadelphia, PA) recently was approved by the US Food and Drug Administration for the treatment of patients with CD33-positive acute myeloid leukemia in first relapse, age 60 years or older, who are not considered candidates for other types of cytotoxic chemotherapy. In combined phase II studies of 142 patients with CD33-positive acute myeloid leukemia in first relapse, Mylotarg monotherapy was associated with a 30% overall response rate. Although treated patients had relatively high incidences of myelosuppression, hyperbilirubinemia, and elevated hepatic transaminases, the incidences of severe mucositis and infections were low compared with what might be expected in association with conventional chemotherapeutic treatment. Preliminary data in pediatric patients also suggest that the immunoconjugate is reasonably well tolerated. Studies of Mylotarg in combination with anthracycline, cytarabine, and agents that inhibit P-glycoprotein are underway.
UI - 11681409
AU - Visani G; Buonamici S; Malagola M; Isidori A; Piccaluga PP; Martinelli
TI - G; Ottaviani E; Grafone T; Baccarani M; Tura S Pulsed ATRA as single therapy restores long-term remission in PML-RARalpha-positive acute promyelocytic leukemia patients: real time quantification of minimal residual disease. A pilot study.
SO - Leukemia 2001 Nov;15(11):1696-700
AD - Department of Hematology, Azienda Ospedale San Salvatore, Pesaro, Italy.
All-trans retinoic acid (ATRA), alone or combined with chemotherapy (CHT) is widely used to induce complete remission (CR) in newly diagnosed acute promyelocytic leukemia (APL). If used alone, ATRA results in a substantial proportion of CRs. To maintain remission further, ATRA is commonly used with cycles of CHT, frequently followed by autologous (auto) or allogeneic (allo) stem cell transplantation (SCT), as early reports have shown that the continuous administration of ATRA as single therapy almost invariably leads to relapse in a short period of time (months). Pharmacokinetic studies have shown that induced resistance to ATRA is frequently suppressed by the intermittent use of the drug. In this study we applied an intermittent therapeutic protocol with ATRA in five APL patients who were either molecularly refractory after combined ATRA/CHT treatment, or relapsed, or at diagnosis, but not eligible for the combination treatment because of previous toxicity. They were treated with ATRA (45 mg/m2/day) for 21 days. The treatment was then prolonged continuously for 1 week every 2 weeks. Molecular analysis was performed by qualitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR). All patients obtained molecular remission, as assessed by qualitative RT-PCR, in a median of 3 months (range 1-15). Quantitative RT-PCR confirmed these data, showing a progressive reduction (1 or 2 logs) to a 'negligible quantity' of PML-RARalpha fusion transcript (ratio PML-RARalpha/ABL x 10(4) ABL < 10(-1)) in all but one patient treated with pulsed ATRA therapy. These data were confirmed with qualitative and quantitative RT-PCR. After a median follow-up of 17 months from the start of ATRA therapy, 4/5 patients (80%) are in continuous complete molecular remission. To our knowledge, this is the first clinical observation that intermittent ATRA therapy (without chemotherapy) is effective not only in inducing but also in maintaining long-term molecular remission in APL patients. This approach could therefore be effective, if confirmed in larger series, in relapsed/refractory patients unsuitable for high-dose therapy and SCT; it may be proposed as induction therapy for selected older APL patients if considered not to be eligible for combined ATRA/CHT due to inadequate performance status or concurrent disease.
UI - 11684284
AU - Koistinen P; Siitonen T; Mantymaa P; Savolainen ER
TI - p53 and redox state in etoposide-induced acute myeloblastic leukemia cell death.
SO - Leuk Res 2001 Dec;25(12):1099-105
AD - Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland. email@example.com
We investigated whether p53, being a redox-sensitive protein, has a role in the responsiveness of AML cells to etoposide. Two subclones of the OCI/AML-2 cell line, the etoposide-sensitive (ES) and the etoposide-resistant (ER), were used as models. Sensitivity to etoposide was measured by trypan blue and annexin V assays. Etoposide-induced peroxide formation was associated with the induction of cell death. Evident expression of mutated p53 was observed in both subclones in basal growth conditions as analysed by Western blotting and flow cytometry. After etoposide exposure for up to 24 hours, some nuclear accumulation of p53 was observed in the ER subclone, as analysed by Western blotting. The conformation of p53, however, was not changed from mutated toward wild-type during exposure in either of the subclones as analysed by flow cytometry. In conclusion, etoposide-induced change in cellular redox state was associated with apoptosis, but was not a sufficient stimulus for p53 to make its conformation active. Thus, mutated p53 seems to have no role in etoposide-induced apoptosis.
UI - 11704841
AU - de The H; Chelbi-Alix MK
TI - APL, a model disease for cancer therapies?
SO - Oncogene 2001 Oct 29;20(49):7136-9
AD - CNRS UPR 9051 Hopital St. Louis 1, avenue C. Vellefaux 75475 Paris Cedex 10, France.
UI - 11704842
AU - Degos L; Wang ZY
TI - All trans retinoic acid in acute promyelocytic leukemia.
SO - Oncogene 2001 Oct 29;20(49):7140-5
AD - Institut Universitaire d'Hematologie, Saint Louis Hospital (AP-HP) 1, avenue Claude Vellefaux, 75010 Paris, France. firstname.lastname@example.org
All trans retinoic acid (ATRA) is able to induce complete remission (CR) in almost all patients with acute promyelocytic leukemia (APL) through in vivo differentiation of APL blasts. However, it cannot eliminate the leukemic clone and to be effective must be used in combination with anthracycline-based chemotherapy. Experience accumulated over the last 10 years has clearly shown that the combination of ATRA and chemotherapy gives better survival in newly diagnosed APL than chemotherapy alone because of fewer relapses and a higher CR rate experienced by these patients. It is also strongly suggested that maintenance treatment with ATRA, and possibly in combination with low-dose chemotherapy, can further reduce the incidence of relapse. Overall, more than 90% of patients with newly diagnosed APL can achieve CR and about 75% can be cured by the combination of ATRA and chemotherapy.
UI - 11722411
AU - Petti MC; Pinazzi MB; Diverio D; Romano A; Petrucci MT; De Santis S;
TI - Meloni G; Tafuri A; Mandelli F; Lo Coco F Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676).
SO - Br J Haematol 2001 Oct;115(1):63-5
AD - Department of Cellular Biotechnology and Haematology, University La Sapienza, Roma, Italy.
We report a patient with acute promyelocytic leukaemia (APL) who received two doses of gemtuzumab ozogamicin for advanced disease. Previous treatments included front-line all-trans retinoic acid and anthracyclines, polychemotherapy consolidation, salvage chemotherapy for the first relapse followed by autologous stem cell transplantation (ASCT), arsenic trioxide for the second relapse followed by a second ASCT and then high-dose methotrexate for more advanced systemic disease with central nervous system involvement. The patient achieved prolonged haematological and molecular remission after monotherapy with gemtuzumab ozogamicin given at the time of the third relapse.
UI - 11713460
AU - Trebo MM; Mann G; Gadner H
TI - And the sun keeps shining.
SO - J Pediatr 2001 Nov;139(5):753
AD - Children 5 Cancer Research Institute, St Anna Kinderspital, Kinderspitalgasse, 61090, Vienna, Austria.
UI - 11719356
AU - List AF; Kopecky KJ; Willman CL; Head DR; Persons DL; Slovak ML; Dorr R;
TI - Karanes C; Hynes HE; Doroshow JH; Shurafa M; Appelbaum FR Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study.
SO - Blood 2001 Dec 1;98(12):3212-20
AD - Southwest Oncology Group, Operations Office, 14980 Omicron Dr, San Antonio, TX, USA. email@example.com
Cyclosporine A (CsA) inhibits P-glycoprotein (Pgp)-mediated cellular export of anthracyclines at clinically achievable concentrations. This randomized controlled trial was performed to test the benefit of CsA addition to treatment with cytarabine and daunorubicin (DNR) in patients with poor-risk acute myeloid leukemia (AML). A total of 226 patients were randomly assigned to sequential treatment with cytarabine and infusional DNR with or without intravenous CsA. Remitting patients received one course of consolidation chemotherapy that included DNR with or without CsA as assigned during induction. Addition of CsA significantly reduced the frequency of resistance to induction chemotherapy (31% versus 47%, P =.0077). Whereas the rate of complete remission was not significantly improved (39% versus 33%, P =.14), relapse-free survival (34% versus 9% at 2 years, P =.031) and overall survival (22% versus 12%, P =.046) were significantly increased with CsA. The effect of CsA on survival was greatest in patients with moderate or bright Pgp expression (median 12 months with CsA versus 4 months for controls) compared to patients with absent or low Pgp expression (median 6 months in both arms). The frequency of induction deaths was 15% with CsA and 18% in controls. Steady-state serum concentrations of DNR (P =.0089) and daunorubicinol (P <.0001) were significantly higher in CsA-treated patients. Survival (P =.0003) and induction response (P =.028) improved with increasing DNR concentration in CsA-treated patients but not in controls, suggesting a targeted interaction by CsA to enhance anthracycline cytotoxicity. These results indicate that addition of CsA to an induction and consolidation regimen containing infusional DNR significantly reduces resistance to DNR, prolongs the duration of remission, and improves overall survival in patients with poor-risk AML.
UI - 11719375
AU - Montagna D; Maccario R; Locatelli F; Rosti V; Yang Y; Farness P; Moretta
TI - A; Comoli P; Montini E; Vitiello A Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy.
SO - Blood 2001 Dec 1;98(12):3359-66
AD - BMT Laboratory and BMT Units, Department of Pediatrics, Laboratory of Organ Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Italy.
Adoptive cellular immunotherapy has proven to be a successful approach in preventing and curing cytomegalovirus infection and Epstein-Barr virus-associated lymphomas after bone marrow transplantation. Translation of this approach for preventing leukemia relapse after bone marrow transplantation might require ex vivo priming and long-term maintenance of leukemia blast-specific T cells. To accomplish this goal, procedures were optimized for the in vitro priming of naive CD8 using dendritic cells activated by CD40 ligation, interleukin-12 (IL-12), and IL-7. Using T lymphocytes and dendritic cells obtained from HLA-matched allogeneic bone marrow transplantation donors and leukemia blasts as a source of tumor antigens, anti-acute myeloid leukemia cytotoxic T lymphocytes (CTLs) were induced. In these experiments, it was found that though it is possible to induce CTLs using immature dendritic cells, IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD4 T cells in the priming phase. Using this approach, long-term antileukemia CTL lines could be generated from 4 of 4 bone marrow donors. Because this procedure does not require definition of the target antigen and because it selects responding cells from a virgin T-cell repertoire, its general application is suggested in adoptive immunotherapy and in the definition of tumor rejection antigens.
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, Hjpital 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.
UI - 11694116
AU - Barbey JT; Soignet S
TI - Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia.
SO - Ann Intern Med 2001 Nov 6;135(9):842-3
UI - 11713382
AU - Keung YK; Morgan D; Cobos E
TI - Cocaine-contaminated allogeneic bone marrow transplantation.
SO - Acta Haematol 2001;106(3):136-7
AD - Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Tex., USA. firstname.lastname@example.org
Should a person with history of drug addiction be categorically denied as a bone marrow donor? The answer to the question is controversial. We report a case of allogeneic bone marrow transplantation for refractory acute myeloid leukemia preceded by essential thrombocythemia. The donor used cocaine and marijuana the night before the bone marrow harvest. Copyright 2001 S. Karger AG, Basel
UI - 11525581
AU - Rule S; Poirer V; Singer C
TI - Management of acute myeloid leukaemia. A regional audit in the south and west of the United Kingdom.
SO - Clin Med 2001 Jul-Aug;1(4):313-6
AD - Department of Haematology, Derriford Hospital, Plymouth, Devon. email@example.com
In a retrospective audit data were collected on all 231 patients from 26 hospitals diagnosed with AML in the south and west region of the UK in 1996. Their median age at diagnosis was 67 years. Sixty one percent (142/231) of patients were treated with chemotherapy; most of the rest received blood product support only; and 7% (15) had no treatment at all. Sixty eight percent of patients aged under 60 years were treated in a clinical trial compared with 24% of patients over 60. The major reasons given for not entering patients in a trial were ineligibility in the younger cohort and poor performance status in the older group. Twenty elderly patients (12.5%) refused to be entered in a trial. In an unselected cohort of patients with AML the accrual into clinical trials is impressively high for patients under 60 years. However, this is a disease of the elderly and comparable enrolment is not seen with elderly patients despite being managed by the same haematologists. If the percentage of patients entered into trials is to be defined as a quality standard, then it is important for those trials to be relevant to the population being treated.
UI - 2031969
AU - Willemze R; Fibbe WE; Kluin-Nelemans JC; Falkenburg JH; Richel DJ;
TI - Peters WG; den Ottolander GJ; Brand A; Zwaan FE Bone marrow transplantation or chemotherapy as post-remission treatment of adult acute myelogenous leukemia.
SO - Ann Hematol 1991 Feb-Mar;62(2-3):59-63
AD - Department of Hematology, Leiden University Medical Center, The Netherlands.
We compared three consolidation regimens in patients with acute myelogenous leukemia in first remission. Thirty-four patients received only intensive consolidation chemotherapy (SIC); 28 patients were scheduled to undergo an autologous bone marrow transplant (auto-BMT) and 44 patients an allogeneic BMT (allo-BMT). Twenty-seven of them were referred in first remission for allo-BMT. Nineteen patients achieved a complete remission after salvage treatment. All other patients obtained a remission after one or two courses of a standard combination of cytosine arabinoside and daunorubicin. Except for the patients who were referred in remission, all patients received intermediate dose cytosine arabinoside and amsacrine as a first consolidation treatment. The median ages of the three groups were 48 (SIC), 39 (auto-BMT) and 33 years (allo-BMT). Two patients relapsed before auto-BMT and 1 before allo-BMT. The median interval from the date of complete remission to the auto- or allo-BMT was 3 months. In total, 80% of the patients of the SIC group relapsed, compared to 50% of the patients belonging to the auto-BMT group and 35% of the 44 patients who were scheduled to receive an allo-BMT. The overall median disease-free survival was 14 months, 30% of the patients being