National Cancer Institute®
Last Modified: July 1, 2002
UI - 12065553
AU - Perel Y; Auvrignon A; Leblanc T; Vannier JP; Michel G; Nelken B;
TI - Gandemer V; Schmitt C; Lamagnere JP; De Lumley L; Bader-Meunier B; Couillaud G; Schaison G; Landman-Parker J; Thuret I; Dalle JH; Baruchel A; Leverger G; Group LAME of the French Society of Pediatric Hematology and Immunology Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucamie Aique Myeloide Enfant.
SO - J Clin Oncol 2002 Jun 15;20(12):2774-82
AD - Unite d'Onco-Hematologie, Departement de Pediatrie, Hopital des Enfants, Groupe Hospitalier Pellegrin, Centres Hospitalo-Universitaires de Bordeaux, France. email@example.com
PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucamie Aique Myeloide Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/- 15%; P =.04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.
UI - 11896426
AU - Linker CA; Damon LE; Ries CA; Navarro WA; Case D; Wolf JL
TI - Autologous stem cell transplantation for advanced acute myeloid leukemia.
SO - Bone Marrow Transplant 2002 Feb;29(4):297-301
AD - University of California, San Francisco, CA, USA.
We studied the efficacy of a two-step approach to autologous stem cell transplantation for patients with advanced acute myeloid leukemia. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) twice daily for 4 days plus etoposide 40 mg/kg by continuous infusion over the same 4 days. Peripheral blood stem cells were collected under granulocyte colony-stimulating factor (G-CSF) stimulation during recovery from this chemotherapy. Step 2, autologous stem cell transplantation, utilized the preparative regimen of oral busulfan 16 mg/kg followed by etoposide 60 mg/kg i.v. During step 1, there were no treatment-related deaths among 28 patients, but two patients did not proceed to transplantation because of failure of mobilization. A median CD34+ dose (x10(6)/kg) of 13.6 was collected. Of 26 patients undergoing autologous transplant, there was one treatment-related death and 12 relapses. With a median follow-up of 5.4 years, 5 year event-free survival (EFS) of all patients entered is 54%. The most important prognostic factor was cytogenetic changes. All seven patients with t(15,17) remained in long-term remission whereas EFS for other patients was 38%. We conclude that this two-step approach to autologous transplantation produces excellent stem cell yields, allows a high percentage of patients to receive the intended therapy, and provides effective treatment.
UI - 11903277
AU - Wu H
TI - Tretinoin for the treatment of acute promyelocytic leukemia.
SO - Cancer Pract 2002 Mar-Apr;10(2):109-11
AD - University of California Medical Center, Department of Clinical Pharmacy, San Francisco, California, USA.
UI - 12028058
AU - Shehata N; Walker IR; Carter RC; Neame PB; Leber B
TI - Prolonged complete remission in two cases of acute promyelocytic leukaemia treated with atra alone.
SO - Br J Haematol 2002 Jun;117(3):768
UI - 11195406
AU - Radich J; Sievers E
TI - New developments in the treatment of acute myeloid leukemia.
SO - Oncology (Huntingt) 2000 Nov;14(11A):125-31
AD - Clinical Research Division, Program in Genetics and Genomics, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. firstname.lastname@example.org
Curative therapy for acute myeloid leukemia (AML) remains unsatisfactory. However, three recent advances may play an important role in determining how AML is treated in the near future. First, the development of targeted antibody therapy using the anti-CD33-calicheamicin conjugate (gemtuzumab ozogamicin, Mylotarg) represents a novel targeted approach to the killing of leukemia cells. Second, modern molecular methods have improved our ability to identify minimal residual disease (MRD) in patients who appear to be in remission. These methods will allow physicians to tailor therapy, offering, for example, more intensive therapy to patients who harbor MRD. Lastly, the development of microarray gene expression technology allows for the simultaneous study of thousands of genes. With this technology, we may determine the genes responsible for the biological properties of treatment response and relapse in leukemia patients.
UI - 11342449
AU - van Der Velden VH; te Marvelde JG; Hoogeveen PG; Bernstein ID;
TI - Houtsmuller AB; Berger MS; van Dongen JJ Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells.
SO - Blood 2001 May 15;97(10):3197-204
AD - Department of Immunology, Erasmus University Rotterdam and University Hospital Rotterdam, The Netherlands. email@example.com
Antibody-targeted chemotherapy is a promising therapy in patients with acute myeloid leukemia (AML). In a phase II study of Mylotarg (CMA-676, gemtuzumab ozogamicin), which consists of a CD33 antibody linked to calicheamicin, saturation and internalization by leukemic and normal myeloid cells were analyzed in 122 patients with relapsed AML. Peripheral blood samples were obtained just before and 3 and 6 hours after the start of the first and second Mylotarg treatment cycles. Within 3 to 6 hours after infusion, near complete saturation of CD33 antigenic sites by Mylotarg was reached for AML blasts, monocytes, and granulocytes, whereas Mylotarg did not bind to lymphocytes. Saturation levels prior to the start of the second Mylotarg treatment cycle were significantly increased compared with background levels before the start of the first cycle. This apparently was caused by remaining circulating Mylotarg from the first treatment cycle (approximately 2 weeks earlier). On binding of Mylotarg to the CD33 antigen, Mylotarg was rapidly internalized, as determined by the decrease in maximal surface membrane Mylotarg binding. Internalization of Mylotarg was also demonstrated in myeloid cells in vitro and was confirmed by confocal laser microscopy. In vitro studies using pulse labeling with Mylotarg showed a continuous renewed membrane expression of CD33 antigens, which can significantly increase the internalization process and thereby the intracellular accumulation of the drug. Finally, Mylotarg induced dose-dependent apoptosis in myeloid cells in vitro. These data indicate that Mylotarg is rapidly and specifically targeted to CD33(+) cells, followed by internalization and subsequent induction of cell death.
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. firstname.lastname@example.org
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 - 11474494
AU - Larson RA
TI - Current use and future development of gemtuzumab ozogamicin.
SO - Semin Hematol 2001 Jul;38(3 Suppl 6):24-31
AD - University of Chicago, Chicago, IL 60637, USA.
The antigen CD33 is expressed on blast cells in 80% to 90% of acute myeloid leukemia (AML) cases but, importantly, is not expressed on pluripotent hematopoietic stem cells or on nonhematologic cells. Gemtuzumab ozogamicin (CMA-676) uses a recombinant humanized anti-CD33 monoclonal IgG4 antibody to deliver the potent cytotoxin, calicheamicin, into cells. Three multicenter trials have evaluated the efficacy and safety of gemtuzumab ozogamicin as a single agent in 142 patients with CD33+ AML in untreated first relapse. The median age was 61 years (range, 22 to 84 years), none had prior myelodysplasia, and all had had a first complete remission lasting > or = 3 months. Two doses of 9 mg/m2 were given 14 days apart by 2-hour intravenous infusion. The overall response rate was 30% (ie, < or = 5% blasts remaining in the bone marrow, neutrophils > or = 1,500/microL, and red blood cell and platelet transfusion independence). There was no significant difference in response rate between patients less than 60 years of age and those > or = 60 years old (34% v 26%, respectively) or between patients whose first remission had lasted less than 12 months or > or = 12 months (28% v 32%, respectively). Overall survival was 31% at 1 year; median survival was 5.9 months. Median relapse-free survival was 6.8 months. An infusion-related syndrome (chills, fever, rigors, nausea, hypotension, and pain) was common. Severe myelosuppression occurred in all patients, but severe mucositis (4%) and infections (23%) were relatively infrequent. Severe hyperbilirubinemia (23%) and elevated hepatic transaminases (18%) were usually transient. Among all 142 patients, the median total hospitalization was 24 days; 16% of patients required < or = 7 days in hospital. Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy. Copyright 2001 by W.B. Saunders Company.
UI - 11511025
AU - McGavin JK; Spencer CM
TI - Gemtuzumab ozogamicin.
SO - Drugs 2001;61(9):1317-22; discussion 1323-4
AD - Adis International Limited, Mairangi Bay, Auckland, New Zealand. email@example.com
Gemtuzumab ozogamicin is a humanised monoclonal IgG4 antibody, linked to a cytotoxic calicheamicin derivative. It effects cell necrosis by specifically targeting the CD33 antigen which is expressed on the surface of leukaemic cell blasts in more than 90% of patients with acute myeloid leukaemia (AML), but is not present on normal stem cells. Therapy with gemtuzumab ozogamicin (2 doses of 9 mg/m2) in 3 noncomparative studies produced complete remission in 16% of adult patients with AML in first relapse, and complete remission with incomplete platelet recovery in an additional 13% of patients. Rates of remission did not differ between those aged less than 60 years and older than 60 years. Many patients were able to receive both doses of gemtuzumab ozogamicin therapy as outpatients. Survival duration was similar between those treated as outpatients and those requiring hospitalisation. About one-third of 11 children and adolescents treated with 2 doses of 9 mg/m2 gemtuzumab ozogamicin in a phase I study showed <5% bone marrow blasts after completion of therapy. The most commonly encountered adverse events in clinical trials with gemtuzumab ozogamicin were myelosuppression, increased levels of hepatic enzymes, infection, fever, bleeding, chills, nausea and vomiting and dyspnoea. No treatment-related renal failure or alopecia was reported.
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 - 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 - 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 - 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 - 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 - 11989187
AU - Anderson S; Files J
TI - Tumor lysis syndrome secondary to Gemtuzumab Ozogamicin in a patient with acute myelogenous leukemia.
SO - J Miss State Med Assoc 2002 Apr;43(4):105-6
AD - Department of Medicine, University of Mississippi Medical Center, USA.
UI - 12010830
AU - Estey EH; Giles FJ; Beran M; O'Brien S; Pierce SA; Faderl SH; Cortes JE;
TI - Kantarjian HM Experience with gemtuzumab ozogamycin ("mylotarg") and all-trans retinoic acid in untreated acute promyelocytic leukemia.
SO - Blood 2002 Jun 1;99(11):4222-4
AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston 77030, USA. email@example.com
We administered gemtuzumab ozogamycin ("mylotarg"; 9 mg/m(2) day 1 or 5) and all-trans retinoic acid (ATRA) to 19 patients with untreated acute promyelocytic leukemia (APL). There were 3 patients who also received idarubicin because of a white blood cell (WBC) count of more than 30 000/microL. In complete remission (CR), patients were to receive 8 courses of mylotarg (9 mg/m(2) every 4 to 5 weeks) and ATRA; idarubicin was added only for persistent or recurrent polymerase chain reaction (PCR) positivity. The CR rate was 16/19 (84%). All 12 patients tested to date were PCR-negative 2 to 4 months from CR date; none of the 7 patients evaluated subsequently have reverted to PCR positivity (median follow-up in CR was 5 months, up to 14 months). Mylotarg was well tolerated. A median of 5 post-CR courses have been given to date with 3 patients having currently received 8 post-CR courses, and 4 patients receiving 7 post-CR courses. Mylotarg appears active in APL, and repeated administration is feasible.
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.
UI - 11925533
AU - Parisi E; Draznin J; Stoopler E; Schuster SJ; Porter D; Sollecito TP
TI - Acute myelogenous leukemia: advances and limitations of treatment.
SO - Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Mar;93(3):257-63
AD - Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Acute myelogenous leukemia (AML) describes a group of related hematologic malignancies that are being approached therapeutically from several perspectives. Conventional chemotherapeutic agents, such as anthracyclines and cytosine arabinoside (Ara-C), are useful in treating AML but now appear to have reached their maximum potential. Newer therapeutic approaches to AML have recently focused on immune-based therapy through monoclonal antibodies that target and destroy malignant cells via specific cell receptors. One such agent is gemtuzumab (CMA-676), an agent that targets the CD33 antigen on malignant myeloid cells. Initial studies have shown significant anticancer activity. We will discuss traditional and newer therapeutic approaches to AML and review the role of monoclonal antibody based therapies for patients with AML. A case of a 30-year-old man with refractory AML who was treated with gemtuzumab will be mentioned, highlighting potential applications and possible limitations to this novel therapy. Despite the effective reduction in the number of malignant cells in bone marrow, gemtuzumab ineffectively treated extramedullary leukemic gingival infiltrate. Regardless of limitations, monoclonal-based therapy offers an exciting and potentially safer adjunctive therapy for patients with AML.
UI - 12094255
AU - Porrata LF; Litzow MR; Tefferi A; Letendre L; Kumar S; Geyer SM;
TI - Markovic SN Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia.
SO - Leukemia 2002 Jul;16(7):1311-8
AD - Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.
UI - 12057059
AU - Douer D
TI - Acute promyelocytic leukemia.
SO - Curr Treat Options Oncol 2000 Apr;1(1):31-40
AD - Division of Hematology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA 90033, USA.
The treatment of acute promyelocytic leukemia (APL) is different from other subtypes of acute myelocytic leukemia (AML). All trans-retinoic acid (ATRA) is an essential component of the standard remission induction for all newly diagnosed APL patients. Remission induction with ATRA and chemotherapy given concurrently appears to be associated with fewer relapses. With further consolidation chemotherapy without high-dose cytosine arabinoside, the disease-free survival rate can reach 70% to 80%, and many of these patients are cured, more so than in any other AML subtype. APL is especially sensitive to anthracyclines, which should be included in the chemotherapy cycles at a higher dose than in other AML subtypes. Maintenance with low-dose chemotherapy (oral daily 6-mercaptopurine with weekly methotrexate) or ATRA further improves the long-term outcome. New approaches are also available for relapsing patients, although the optimal treatment is unknown. Patients who did not receive oral ATRA in first relapse can be treated with this agent, as can first relapsing patients who have been off the drug for more than 1 year. Because of poor remission rates, ATRA should not be used in patients with second or subsequent relapses (whether ATRA was given in the past), in patients with relapses early after ATRA discontinuation, or in patients relapsing while on ATRA therapy. Arsenic trioxide can also be used, especially in patients resistant to ATRA. Because arsenic trioxide is still experimental and not yet widely available, patients who are unlikely to respond to ATRA or who unsuccessfully undergo ATRA reinduction should be treated with chemotherapy. Patients in second or subsequent remission induced with ATRA or chemotherapy should receive consolidation chemotherapy. When arsenic trioxide is used for reinduction, the drug should be continued for several cycles; however, adding consolidation chemotherapy might improve the results. Because it is unknown whether APL in second or subsequent remission is curable with salvage therapy, allogeneic hematopoietic stem cell transplantation is often considered for patients with a human leukocyte antigen (HL-A)-identical sibling and autologous transplantation when a donor does not exist. However, compared with the new treatments, the role of transplantation for relapse is unclear. In first remission, there is no role for transplantation. A new liposomal formulation of intravenous ATRA is being investigated and seems effective in late first relapses, and it may be able to induce and maintain first remissions in selected patients without chemotherapy.
UI - 12071940
AU - Tamayose K; Sugimoto K; Ando M; Oshimi K
TI - Mononucleosis syndrome and acute monocytic leukemia.
SO - Eur J Haematol 2002 Apr;68(4):236-8
AD - Department of Hematolgy, Juntendo University School of Medicine, Tokyo, Japan. firstname.lastname@example.org
The association of infectious mononucleosis and an immunocompromised host such as occurs in acute leukemia is reported. The most common cause of infectious mononucleosis is Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Patients with mononucleosis syndrome caused by other agents are rare. We report a case of acute monocytic leukemia (AMoL) who developed varicella zoster virus (VZV) mononucleosis syndrome in the bone marrow recovery phase after myelosuppression due to high-dose cytarabine. Mononuclear leukocytes appearing during the mononucleosis syndrome were very similar to the initial leukemic cells. Varicella zoster virus mononucleosis syndrome was confirmed by delayed herpes zoster rash with dermatomal distribution.
UI - 12016812
AU - Yang J; Han Z; Pei M; Xiao N
TI - [Fatal side-effects of all-trans retinoic acid in the treatment of acute promyelocytic leukemia]
SO - Hunan Yi Ke Da Xue Xue Bao 1999;24(3):293-5
AD - Department of Hematology, Second Affiliated Hospital, Hunan Medical University, Changsha 410011.
Of 82 patients with acute promyelocytic leukemia (APL) who were treated with all-trans retinoic acid (ATRA), 35 developed leukocytosis and 22 fatal side-effects(15 with retinoic acid syndrome and 7 intracranial bleeding). There was a high mortality in the patient with fatal side-effects. The relationship between leukocytosis and fatal side-effects was analyzed and the effect of therapeutic interventions on the development and prognosis of the fatal side-effects was investigated. The results showed that leukocytosis was a risk factor of the development of fatal side-effects in APL treated with ATRA. ATRA combined with small dose of harringtonin in treating APL can reduce the incidence of intracranial bleeding resulted from leukocytosis and corticosteroid can decrease the mortality of retinoic acid syndrome.
UI - 12111790
AU - Tomonari A; Shirafuji N; Iseki T; Ooi J; Nagayama H; Masunaga A; Tojo A;
TI - Tani K; Asano S Acquired pulmonary alveolar proteinosis after umbilical cord blood transplantation for acute myeloid leukemia.
SO - Am J Hematol 2002 Jun;70(2):154-7
AD - Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. email@example.com
Pulmonary alveolar proteinosis (PAP) is a heterogeneous disease that occasionally develops with hematological malignancy. However, PAP in association with hematopoietic stem cell transplantation is quite rare. Here we present the first report of a patient who developed PAP after cord blood transplantation (CBT). A 45-year-old female with AML underwent unrelated CBT. On day +2 after CBT she developed congestive heart failure with diffuse alveolar infiltrates in the bilateral lungs. Despite treatment, the alveolar infiltrates further increased with progression of multiple organ failure (MOF). She died from MOF before hematopoietic recovery on day +27. Post-mortem study revealed that massive amorphous materials positive for periodic acid-Schiff stain filled in the pulmonary alveoli. These findings led to a diagnosis of PAP. The bone marrow was hypocellular without the leukemic cells. The impaired immunity during the period of leukopenia as well as the impaired clearance of surfactant proteins might contribute to the development of PAP. Copyright 2002 Wiley-Liss, Inc.
UI - 12060484
AU - Mandelli F; Avvisati G; Lo Coco F
TI - Advances in the understanding and management of acute promyelocytic leukemia.
SO - Rev Clin Exp Hematol 2002 Mar;6(1):60-71; discussion 86-7
AD - Department of Cellular Biotechnologies and Hematology, University 'La Sapienza', Rome, Italy.
Considerable progress has been made over the past decade in the understanding and management of acute promyelocytic leukemia (APL). At the laboratory level, molecular mechanisms underlying the arrest of differentiation that typically features in this malignancy, have been clarified and currently provide important models for addressing future investigation aimed at releasing the maturation block in other malignancies. In the clinic, advances in the management of APL have converted this rapidly fatal disease into the most frequently curable leukemia in adults. Use of retinoids in combinatorial protocols with anthracycline-based chemotherapy for front line treatment currently results in long-term survival and potential cure in at least 60% of newly diagnosed patients. Even after relapse, the disease is still curable in a high percentage of cases by various approaches including combinations of chemotherapy, retinoids, arsenic trioxide, stem cell transplantation and antibody-targeted chemotherapy. Genetic testing for identification of the disease-specific gene rearrangement and monitoring of residual disease have proved critical in establishing correct diagnosis and better evaluate the response to therapy at the molecular level. Current 'hot' issues for clinical investigation include: (i) better understanding and management of the severe coagulopathy present at diagnosis in most patients; (ii) the definition of risk categories to improve identification of patients at highest risk of relapse and (iii) the translation of successful differentiation therapy to other leukemia subsets.
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.