Monday, December 6, 2004, 02:00 PM
[393] Use of All-Transretinoic Acid (ATRA) + Arsenic Trioxide (ATO) To Eliminate or Minimize Use of Chemotherapy (CT) in Untreated Acute Promyelocytic Leukemia (APL). Session Type: Oral Session
Elihu H. Estey, Guillermo Garcia-Manero, Alexandra Ferrajoli, Stefan Faderl, Srdan Verstovsek, Hagop Kantarjian. Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Current therapy cures most patients (pts) with newly diagnosed APL. Therefore, by analogy to childhood acute lymphoblastic leukemia, focus reduction of therapy-associated toxicity appears appropriate. Such reduction implies less reliance on anthracyclines, which can, rarely but not inconsequentially, cause sepsis, myelodysplastic syndromes, and cardiotoxicity. An obstacle to eliminating anthracylines is the belief that ATRA-induced remissions are transient, unless anthracyclines are also given. We examined whether combining ATRA and ATO might allow elimination of CT. ATO (0.15 mg/kg/day) began 10 days after ATRA (45 mg/m2 twice daily). In CR, both drugs were to be continued until 6 months from CR date. CT (typically gemtuzumab ozogamycin, GO, 9 mg/m2 one dose) was only to be given (1) during induction (day 1) if the presenting WBC count was > 10,000/ ml, (2) if 2 consecutive polymerase chain reaction (PCR) tests for PML-RARa (sensitivity level 10-4, tests repeated at 2-4 week intervals) were positive 3 months from CR date, or (3) for reversion of a negative PCR test to positive on 2 consecutive occasions as above (molecular relapse). 32 patients (median age 45, 13 with WBC > 10,000 = “high risk”, HR) went on study. The CR rate was 28/32 (88%, 11/13, 85% in HR). Median time to CR was 29 days. Three of the 32 pts died before receiving ATO; APL differentiation syndrome occurred in 5 pts. 25/26 evaluated pts were PCR positive at CR. However, 3 months later, 21/21 were PCR negative, with PCR negativity rates of 17/17, 12/13, 9/10, and 5/5 at, respectively, 6, 9,12, and 12-24 months from CR date. Both molecular relapses subsequently had clinical relapses. No other clinical relapses have occurred, with a median time from CR of 7 months (up to 24 months) in the 26 patients alive in 1st CR. GO was substituted for ATO in 5 patients because of toxicity (arrhythmias in 4, asymptomatic in 3). Among the 29 pts who began ATO, the incidence of arrhythmias was 2/2 in African Americans vs. 2/27 in Caucasians (p = 0.01). Recalling that high-risk pts received CT during induction and excluding pts in whom GO was substituted for ATO because of toxicity, rates of PCR negativity are as follows at 3,6,9,12,and 12-24 months from CR date (rates for high-risk patients in parentheses): 17/17(6/6), 14/14(7/7), 10/11(6/7), 8/9(4/5) and 4/4(3/3). Pending further follow-up, cure of untreated APL without (WBC < 10,000), or with only minimal use (WBC > 10,000) of, CT appears feasible.
Abstract #393 appears in Blood, Volume 104, issue 11, November 16, 2004
Keywords: Anthracycline|Sepsis|Gemtuzumab ozogamicin
Simultaneous Session: Acute Promyelocytic Leukemia (1:30 PM-3:00 PM)
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Monday, December 6, 2004, 02:30 PM
[395] Treatment of Relapsed Acute Promyelocytic Leukemia by Arsenic-Based Strategies without Hematopoietic Stem Cell Transplantation in Hong Kong: A Seven-Year Experience.
Session Type: Oral Session
Wing Y. Au, James C. Chim, Albert K. Lie, Cyrus R. Kumana, Anskar Y. Leung, Eric W. Tse, Shing Y. Ma, Raymond H. Liang, Yok L. Kwong. Department of Medicine, University of Hong Kong, Hong Kong, Pokfulam, Hong Kong
Background: The optimal therapy for relapsed acute promyelocytic leukemia (APL) after arsenic trioxide (As2O3)-induced remission is unclear. Hematopoietic stem cell transplantation (HSCT) is associated with high morbidity and mortality. Moreover, lasting remission is observed in many patients who are not candidates for HSCT, owing to advanced age or lack of donors, implying that HSCT is not mandatory for durable remission. We evaluated our results of an As2O3-based, non-HSCT regimen for patients with relapsed APL.
Materials and methods: Forty-two consecutive patients (18 men, 24 women, median age: 35 years, 12-72) with relapsed (relapse 1, R1=39, R2=3) APL were treated with an-As2O3 based, non-HSCT regimen. The time from last complete remission (CR) was 22 (6-243) months (mo). Initial treatment was As2O3 (10 mg/day) either intravenously (n=16) or orally (n=28) until CR, followed by idarubicin consolidation (6 mg/m2/day x 9). Twenty-five patients received oral-As2O3 maintenance. Post-As2O3 relapses were treated with oral As2O3 + all-trans retinoic acid (ATRA, 45 mg/m2/day) until CR, followed by maintenance (two weeks of ATRA+As2O3 every 2 mo. for 2 years). Post-As2O3/ATRA relapses were treated with oral As2O3+ATRA+ascorbic acid (1g/day) until CR, followed by consolidation/maintenance with the same regimen (2 weeks every 2 mo. for 2 years). Part of the induction and all of the maintenance therapies were given in the outpatient clinic.
Results: Forty-one patients (98%) achieved CR after initial As2O3 treatment. One 72-year old man with XYY syndrome, diabetes and mental retardation died of pneumonia. Thirteen relapses occurred at a median of 15 (6-22) mo. As2O3-maintenance significantly decreased further relapses (3/24 with versus 10/17 without As2O3-maintenance, p=0.003). Two relapses died of cerebral APL before further treatment could be administered. Of eleven patients treated with As2O3+ATRA, 10 achieved CR, 8 of whom have remained in remission (median follow-up: 33 mo.). Two post-As2O3/ATRA relapses achieved CR again with As2O3+ATRA+ascorbic acid, and have remained in remission after maintenance treatment with As2O3+ATRA+ascorbic acid. All patients in continuous remission (n=38) were PML/RARa negative on polymerase chain reaction (sensitivity 10-3 to 10-4).
Conclusion: Our regimen resulted in a leukemia-free-survival of 89.3%. The results suggest that an oral and mainly outpatient As2O3-based, non-HSCT strategy is efficacious for relapsed APL. In terms of survival, costs, treatment side effects and patient tolerance, the results appear to be comparable to, if not more favorable than, other treatment options based on high dose chemotherapy, graft-versus-leukemia effect, or anti-myeloid antibody therapy.
Abstract #395 appears in Blood, Volume 104, issue 11, November 16, 2004
Keywords: Arsenic trioxide|Oral|Acute promyelocytic leukemia
Simultaneous Session: Acute Promyelocytic Leukemia (1:30 PM-3:00 PM)
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Monday, December 6, 2004, 02:45 PM
[396] Treatment of New Cases of Acute Promyelocytic Leukaemia by Arsenic Trioxide.
Session Type: Oral Session
Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Hamidolah Ghaffari, Shahrano Rostami, Yousef Mortazavi, Asadolah Mousavi, Mehrangiz Tootonchi, Mohamad Jahani, Roholah Hosseini, Masoud Iravani, Babak Bahar, Nasser Aghdami. Hematology,Oncology and BMT Research Center, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
Purpose: Arsenic Trioxide approved for treatment of relapsed or refractory APL to ATRA. We studied the effects of Arsenic Trioxide as first line treatment of new cases of APL and their follow up.
Material and methods: we studied 73 new cases of APL diagnosed by morphologic criteria and confirmed by cytogenetic, RT-PCR for PML/RARA and/or FISH and followed patients for MRD by sensitive nested RT-PCR.
Our patients were 30 males and 43 females with median age 30+/- 12. Patients treated by infusion of 0.15mg/kg/d of Arsenic Trioxide to complete remission by morphologic criteria or till day +60. In patients who complete remission achieved, after 28 days rest, again we began Arsenic Trioxide 0.15mg/kg/d for 28 days as consolidation.
Results: complete remission were achieved in 66 patients( 90.4%) and 7 early mortality. Median time to complete remission was 30+/-6.4 days. Most common cause of mortality was APL maturation syndrome ( 4 cases)
Most common toxicities during induction phase were, APL maturation syndrome (10 cases), serositis(6 cases) and hepatotoxicity (19 cases).
63 cases(86.3%) are alive with a median follow up of 17+/-12.65 months. 14 relapses observed in our patients and complete remission achieved with re-treatment by Arsenic trioxide in 11 of them. Also we could control 3 fatal bleeding by infusion of activated factor 7(NovosevenÒ) which stopped hemorrhage .
One year and two/three years survival of patients were 86% and 84%. Most common cause of death was APL maturation syndrome in 4 patients and relapse in 3 cases.Conclusion: Arsenic Trioxide is acceptable as first line treatment of APL and its result is comparable to ATRA with chemotherapy.
Abstract #396 appears in Blood, Volume 104, issue 11, November 16, 2004
Keywords: As2O3|Acute promyelocytic leukemia|Factor VIIa
Simultaneous Session: Acute Promyelocytic Leukemia (1:30 PM-3:00 PM) |
