Español
Questions About Cancer? 1-800-4-CANCER
  • View entire document
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Adult Acute Myeloid Leukemia Treatment (PDQ®)

Untreated Adult AML

The two-drug regimen of cytarabine given in conjunction with daunorubicin (the so-called 7+3 induction therapy) will result in a complete response rate of approximately 65%. Some physicians opt to add a third drug, thioguanine, to this regimen, although little evidence is available to conclude that this three-drug regimen is better therapy. One study suggested that the addition of etoposide during induction therapy may improve response duration.[1] The choice of anthracycline and the dose-intensity of anthracycline may influence the survival of patients with acute myeloid leukemia (AML). Idarubicin appeared to be more effective than daunorubicin, particularly in younger adults, although the doses of idarubicin and daunorubicin may not have been equivalent.[2-5] No significant survival difference between daunorubicin and mitoxantrone has been reported.[6]

In patients aged 60 years and younger, outcomes for those receiving daunorubicin (90 mg/m2/dose, total induction dosing at 270 mg/m2) were superior to those receiving more traditional dosing (45 mg/m2/dose; total dose = 135 mg/m2). Complete remission (CR) rate was 71% versus 57% (P < .001), and median survival was 24 months versus 16 months (P = .003).[7] No randomized comparison data between daunorubicin at 270 mg/m2 and daunorubicin at 180 mg/m2, nor between daunorubicin at 270 mg/m2 and idarubicin, are available. However, two studies examined when idarubicin (36 mg/m2) versus daunorubicin (180 mg/m2 or 240 mg/m2) were administered to elderly patients. While overall survival (OS) was not impacted by the choice of anthracycline, the percentage of long-term disease-free survivors in a mixed-cure model did appear to be impacted (hazard ratio [HR], 0.8; 0.65–0.98).[8] The addition of the CD33-directed immunotoxin gemtuzumab ozogamicin to cytarabine plus anthracycline or clofarabine plus anthracycline in patients aged 51 to 79 years led to a small increase in median survival (25% vs. 20%; HR, 0.87; 95% confidence interval [CI], 0.76–1.00; P = < .05).[9] In contrast, gemtuzumab did not improve the 1-year survival rate of elderly patients receiving low-dose cytarabine, although the CR rate increased from 17% to 30% (odds ratio [OR], 0.48 (0.32–0.73); P = .006).[10]

The role of high-dose cytarabine in induction therapy is controversial; randomized trials have shown prolongation of disease-free survival (DFS) [11,12] or no effect [13,14] compared with conventionally dosed cytarabine-based induction chemotherapy. Post hoc analyses of two negative trials suggested potential benefit for the intensified therapy in subsets of patients at high risk for treatment failure;[13,14] however, an analysis of a subset of patients with complex cytogenetic abnormalities treated in a randomized multicenter trial in Germany showed improvement in CR rate with minimal improvement in event-free survival (EFS) (CR, 56% vs. 23%; P = .04; median EFS, 1 month vs. 2 months; P = .04).[15][Level of evidence: 1iiDii]

AML arising from myelodysplasia or secondary to previous cytotoxic chemotherapy has a lower rate of remission than de novo AML. A retrospective analysis of patients undergoing allogeneic bone marrow transplantation (BMT) in this setting showed that the long-term survival for such patients was identical regardless of whether or not patients had received remission induction therapy (DFS was approximately 20%). These data suggest that patients with these subsets of leukemia may be treated primarily with allogeneic BMT if their overall performance status is adequate, potentially sparing patients the added toxic effect of induction chemotherapy.[16][Level of evidence: 3iiiDii]

Older adults who decline intensive remission induction therapy or are considered unfit for intensive remission induction therapy may derive benefit from low-dose cytarabine, administered twice daily for 10 days in cycles repeated every 4 to 6 weeks. The CR rate using this regimen was 18% compared with 1% for patients treated with hydroxyurea (P = .006).[17] Survival with low-dose cytarabine was better than survival was with hydroxyurea (OR, 0.60; 95% CI, 0.44–0.81; P = .009).[17][Level of evidence: 1iiA] The hypomethylating agents decitabine and azacitidine are used commonly in this population of older adults, particularly in the United States. Although approval of the drugs by the U.S. Food and Drug Administration is for a myelodysplastic syndrome indication, the registration studies leading to approval included patients with 20% to 30% myeloblasts, or what would now be considered oligoblastic AML.[18,19]

One phase III trial randomly assigned 485 AML patients older than 65 years to receive decitabine (n=242) or their preferred choice (n=243) of either supportive care (n=28) or low-dose cytarabine (n=215). Although rates of CR + CRp (CR with incomplete platelet recovery) were more than double in the decitabine arm (17.8%) compared with the treatment-choice arm (7.8%) (P = .001), median OS was not significantly improved for patients receiving decitabine (7.7 months) compared with the treatment of choice (5.0 months) (HR for death for decitabine, 0.85; 95% CI, .69–1.04; P = .11).[20]

Preliminary results from a phase III trial randomly assigned AML patients older than 65 years to azacitidine compared with conventional care regimens of best supportive care, low-dose cytarabine, and 7+3 AML-type induction chemotherapy and similarly showed a nonsignificant difference in median OS for patients receiving azacitidine (10.4 months) versus conventional care (6.5 months) (HR for death for azacitidine, 0.84; 95% CI, .69–1.02; (P = .08).[21]

In sum, low-dose cytarabine, decitabine, azacitidine, or best supportive care can be considered equivalently effective treatment approaches for older AML patients who decline traditional, 7+3 induction chemotherapy.

Supportive care during remission induction treatment should routinely include red blood cell and platelet transfusions when appropriate.[22,23] Empiric broad spectrum antimicrobial therapy is an absolute necessity for febrile patients who are profoundly neutropenic.[24,25] Careful instruction in personal hygiene, dental care, and recognition of early signs of infection are appropriate in all patients. Elaborate isolation facilities (including filtered air, sterile food, and gut flora sterilization) are not routinely indicated but may benefit transplant patients.[26,27] Rapid marrow ablation with consequent earlier marrow regeneration decreases morbidity and mortality. Prophylactic oral antibiotics may be appropriate in patients with expected prolonged, profound granulocytopenia (<100/mm3 for 2 weeks).[28] Norfloxacin and ciprofloxacin have been shown to decrease the incidence of gram-negative infection and time to first fever in randomized trials. The combination of ofloxacin and rifampin has proven superior to norfloxacin in decreasing the incidence of documented granulocytopenic infection.[29-31] Serial surveillance cultures may be helpful in such patients to detect the presence or acquisition of resistant organisms.

A long-term follow-up of 30 patients who had AML that was in remission for at least 10 years has demonstrated a 13% incidence of secondary malignancies. Of 31 long-term female survivors of AML or acute lymphoblastic leukemia younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred.[32]

Treatment options for remission-induction therapy

  1. One of the following equivalent combination chemotherapy regimens:
    • Cytarabine plus daunorubicin.[33,34]
    • Cytarabine plus idarubicin.[2-5]
    • Cytarabine plus mitoxantrone.[35]
    • Dose-intensive cytarabine-based induction therapy.[11,12]
    • Cytarabine plus daunorubicin plus thioguanine.[36]
  2. Treatment of central nervous system leukemia, if present:
    • Intrathecal cytarabine or methotrexate.
  3. Clinical trials.

Acute Promyelocytic Leukemia

Special consideration must be given to induction therapy for acute promyelocytic leukemia (APL). Oral administration of tretinoin (all-trans-retinoic acid [ATRA]); 45 mg/mm2/day) can induce remission in 70% to 90% of patients with M3 AML. (ATRA is not effective in patients with AML that resembles M3 morphologically but does not demonstrate the t(15;17) or typical PML-RARA gene rearrangement.)[37-43] ATRA induces terminal differentiation of the leukemic cells followed by restoration of nonclonal hematopoiesis. Administration of ATRA leads to rapid resolution of coagulopathy in most patients, and heparin administration is not required in patients receiving ATRA. However, randomized trials have not shown a reduction in morbidity and mortality during ATRA induction when compared with chemotherapy. Administration of ATRA can lead to hyperleukocytosis and a syndrome of respiratory distress now known as the differentiation syndrome. Prompt recognition of the syndrome and aggressive administration of steroids can prevent severe respiratory distress.[44] The optimal management of ATRA-induced hyperleukocytosis has not been established; neither has the optimal postremission management of patients who receive ATRA induction. However, two large cooperative group trials have demonstrated a statistically significant relapse-free and OS advantage to patients with M3 AML who receive ATRA at some point during their antileukemic management.[45,46]

Studies performed in the 1990s demonstrated that OS rates improved in patients receiving ATRA in addition to chemotherapy.[47,48]

The C9710 (NCT00003934) trial randomly assigned patients receiving ATRA and anthracyclines to two cycles of consolidation with or without arsenic trioxide (ATO). Event-free survival (EFS), the primary endpoint, was significantly better for patients assigned to receive ATO consolidation, with an 80% EFS rate compared with a 63% EFS rate at 3 years (stratified log-rank test, P < .0001). The secondary endpoint, survival, was better in the ATO arm, with an 86% survival rate compared with an 81% survival rate at 3 years (P = .059) The inclusion of ATO led to outcomes for higher-risk patients that were equivalent to the outcomes for lower-risk patients.[49] A phase II study showed that incorporation of ATO in the primary management of APL patients could reduce the total amount of therapy administered.[50]

Investigators at the University of Texas MD Anderson Cancer Center used an ATO-based regimen, which included gemtuzumab ozogamicin (GO) as the only cytotoxic drug.[51] Patients received ATRA plus ATO induction; patients also received a dose of GO if the WBC was greater than 10,000/mm3 on presentation or rose to over 30,000/mm3 during induction. Patients in remission received alternating months of ATO and ATRA for a total of seven cycles; GO was substituted if either ATO or ATRA were discontinued as a result of toxicity. Eighty-two patients were treated; seven patients died during induction, the remainder achieved remission. Three patients relapsed and four patients died during remission; thus EFS was approximately 76%.

This approach was investigated in a randomized, noninferiority trial that compared ATO plus ATRA with an ATRA-anthracycline-based regimen in patients with lower-risk APL. With median follow-up of 34.4 months, 2-year EFS rates were 97% in the ATRA-ATO group and 86% in the ATRA-chemotherapy group (95% CI for the difference, 2%–22%). OS was also better with ATRA-ATO (P = .02).[52]

Most current regimens for the treatment of APL include some form of maintenance therapy, particularly for patients with higher-risk APL. A meta-analysis of randomized trials has indicated that maintenance clearly improves DFS but not OS; however, these studies did not include ATO-containing trials.

Treatment options

  1. ATRA plus ATO.
  2. ATRA plus anthracycline, followed by ATO-based consolidation therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated adult acute myeloid leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

  1. Bishop JF, Lowenthal RM, Joshua D, et al.: Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Blood 75 (1): 27-32, 1990. [PUBMED Abstract]
  2. Wiernik PH, Banks PL, Case DC Jr, et al.: Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 79 (2): 313-9, 1992. [PUBMED Abstract]
  3. Vogler WR, Velez-Garcia E, Weiner RS, et al.: A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. J Clin Oncol 10 (7): 1103-11, 1992. [PUBMED Abstract]
  4. Berman E, Heller G, Santorsa J, et al.: Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood 77 (8): 1666-74, 1991. [PUBMED Abstract]
  5. Mandelli F, Petti MC, Ardia A, et al.: A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer 27 (6): 750-5, 1991. [PUBMED Abstract]
  6. Arlin Z, Case DC Jr, Moore J, et al.: Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group. Leukemia 4 (3): 177-83, 1990. [PUBMED Abstract]
  7. Fernandez HF, Sun Z, Yao X, et al.: Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 361 (13): 1249-59, 2009. [PUBMED Abstract]
  8. Gardin C, Chevret S, Pautas C, et al.: Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol 31 (3): 321-7, 2013. [PUBMED Abstract]
  9. Burnett AK, Russell NH, Hills RK, et al.: Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 30 (32): 3924-31, 2012. [PUBMED Abstract]
  10. Burnett AK, Hills RK, Hunter AE, et al.: The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison. Leukemia 27 (1): 75-81, 2013. [PUBMED Abstract]
  11. Bishop JF, Matthews JP, Young GA, et al.: A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 87 (5): 1710-7, 1996. [PUBMED Abstract]
  12. Geller RB, Burke PJ, Karp JE, et al.: A two-step timed sequential treatment for acute myelocytic leukemia. Blood 74 (5): 1499-506, 1989. [PUBMED Abstract]
  13. Weick JK, Kopecky KJ, Appelbaum FR, et al.: A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood 88 (8): 2841-51, 1996. [PUBMED Abstract]
  14. Büchner T, Hiddemann W, Wörmann B, et al.: Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. Blood 93 (12): 4116-24, 1999. [PUBMED Abstract]
  15. Schoch C, Haferlach T, Haase D, et al.: Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients. Br J Haematol 112 (1): 118-26, 2001. [PUBMED Abstract]
  16. Anderson JE, Gooley TA, Schoch G, et al.: Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. Blood 89 (7): 2578-85, 1997. [PUBMED Abstract]
  17. Burnett AK, Milligan D, Prentice AG, et al.: A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 109 (6): 1114-24, 2007. [PUBMED Abstract]
  18. Silverman LR, Demakos EP, Peterson BL, et al.: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20 (10): 2429-40, 2002. [PUBMED Abstract]
  19. Kantarjian H, O'brien S, Cortes J, et al.: Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer 106 (5): 1090-8, 2006. [PUBMED Abstract]
  20. Kantarjian HM, Thomas XG, Dmoszynska A, et al.: Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 30 (21): 2670-7, 2012. [PUBMED Abstract]
  21. Itzykson R, Thépot S, Berthon C, et al.: Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res 39 (2): 124-30, 2015. [PUBMED Abstract]
  22. Slichter SJ: Controversies in platelet transfusion therapy. Annu Rev Med 31: 509-40, 1980. [PUBMED Abstract]
  23. Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 (3): 529-34, 1986. [PUBMED Abstract]
  24. Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161 (3): 381-96, 1990. [PUBMED Abstract]
  25. Rubin M, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 (2): 167-84, 1988. [PUBMED Abstract]
  26. Armstrong D: Symposium on infectious complications of neoplastic disease (Part II). Protected environments are discomforting and expensive and do not offer meaningful protection. Am J Med 76 (4): 685-9, 1984. [PUBMED Abstract]
  27. Sherertz RJ, Belani A, Kramer BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 83 (4): 709-18, 1987. [PUBMED Abstract]
  28. Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N Engl J Med 304 (18): 1057-62, 1981. [PUBMED Abstract]
  29. Karp JE, Merz WG, Hendricksen C, et al.: Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 106 (1): 1-7, 1987. [PUBMED Abstract]
  30. Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. The GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Ann Intern Med 115 (1): 7-12, 1991. [PUBMED Abstract]
  31. Bow EJ, Mandell LA, Louie TJ, et al.: Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group. Ann Intern Med 125 (3): 183-90, 1996. [PUBMED Abstract]
  32. Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001. [PUBMED Abstract]
  33. Yates J, Glidewell O, Wiernik P, et al.: Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60 (2): 454-62, 1982. [PUBMED Abstract]
  34. Dillman RO, Davis RB, Green MR, et al.: A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood 78 (10): 2520-6, 1991. [PUBMED Abstract]
  35. Löwenberg B, Suciu S, Archimbaud E, et al.: Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol 16 (3): 872-81, 1998. [PUBMED Abstract]
  36. Gale RP, Foon KA, Cline MJ, et al.: Intensive chemotherapy for acute myelogenous leukemia. Ann Intern Med 94 (6): 753-7, 1981. [PUBMED Abstract]
  37. Huang ME, Ye YC, Chen SR, et al.: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72 (2): 567-72, 1988. [PUBMED Abstract]
  38. Castaigne S, Chomienne C, Daniel MT, et al.: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood 76 (9): 1704-9, 1990. [PUBMED Abstract]
  39. Warrell RP Jr, Frankel SR, Miller WH Jr, et al.: Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 324 (20): 1385-93, 1991. [PUBMED Abstract]
  40. Chen ZX, Xue YQ, Zhang R, et al.: A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood 78 (6): 1413-9, 1991. [PUBMED Abstract]
  41. Muindi J, Frankel SR, Miller WH Jr, et al.: Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia. Blood 79 (2): 299-303, 1992. [PUBMED Abstract]
  42. Licht JD, Chomienne C, Goy A, et al.: Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood 85 (4): 1083-94, 1995. [PUBMED Abstract]
  43. Gallagher RE, Li YP, Rao S, et al.: Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid. Blood 86 (4): 1540-7, 1995. [PUBMED Abstract]
  44. Frankel SR, Eardley A, Lauwers G, et al.: The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med 117 (4): 292-6, 1992. [PUBMED Abstract]
  45. Fenaux P, Le Deley MC, Castaigne S, et al.: Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood 82 (11): 3241-9, 1993. [PUBMED Abstract]
  46. Tallman MS, Andersen J, Schiffer CA, et al.: Phase III randomized study of all-trans retinoic acid (ATRA) vs daunorubicin (D) and cytosine arabinoside (A) as induction therapy and ATRA vs observation as maintenance therapy for patients with previously untreated acute promyelocytic leukemia (APL). [Abstract] Blood 86 (10 Suppl 1): A-488, 125a, 1995.
  47. Adès L, Guerci A, Raffoux E, et al.: Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood 115 (9): 1690-6, 2010. [PUBMED Abstract]
  48. Sanz MA, Montesinos P, Vellenga E, et al.: Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group. Blood 112 (8): 3130-4, 2008. [PUBMED Abstract]
  49. Powell BL, Moser B, Stock W, et al.: Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood 116 (19): 3751-7, 2010. [PUBMED Abstract]
  50. Gore SD, Gojo I, Sekeres MA, et al.: Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia. J Clin Oncol 28 (6): 1047-53, 2010. [PUBMED Abstract]
  51. Ravandi F, Estey E, Jones D, et al.: Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 27 (4): 504-10, 2009. [PUBMED Abstract]
  52. Lo-Coco F, Avvisati G, Vignetti M, et al.: Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369 (2): 111-21, 2013. [PUBMED Abstract]
  • Updated: April 17, 2015