New Group Research Articles

Acute Promyelocytic Leukemia (APL) Induction Therapy and Incidence of Renal Insufficiency

Background: Survival rates of patients with APL have increased >90% with the introduction of all- trans retinoic acid (ATRA) and arsenic trioxide (ATO). However in addition to infections that are common during leukemia induction, bleeding and differentiation syndrome (DS) are frequently seen and are potentially fatal complications unique to APL. Renal failure is considered to be a manifestation of DS but can also occur secondary to infections. Herein, we report development of renal insufficiency (RI) during induction and outcomes in a cohort of patients managed by our program.Methods: Between 1/2007 and 3/2017, we treated or co-managed a total of 210 patients.Our new group (NG) consists of 138 patients which included, 120 patients treated on a prospective clinical trial in a network of Leukemia treatment centers established in Georgia, South Carolina and neighboring states between July 2013 and May 2016. This program was designed to decrease population wide induction deaths. The other 18 patients were referred to our institution from June 2016 to April 2017 and managed on the same algorithm as the prospective trial. Early Group (EG) consisted of 72 patients between 1/2007 and 5/2013 before initiation of this program.We divided patients into four groups based on the CTCAE v.4.03 classification: Grade I - Creatinine (Cr) rise but less than 1.5 times baseline value; Grade II- Cr greater than 1.5 to 3 times baseline; Grade III- Cr greater than 3 times but less than 6 times baseline and Grade IV - Cr greater than 6 times baseline. Institutional review board approval was obtained and statistics are descriptive.Results: All patients were treated at our institution in the EG while in the NG 62 (45%) were treated at our institution and 76 (55%) were managed in 33 outlying centers. The median age in EG and NG was 45 years (range 18-86) and 53 (range 19-84) and 61% and 54.3% were females respectively. RI of all grades developed in 29 (40%) in the EG and 32 (23 %) in NG. The breakdown in EG vs NG is given in Table1.ATRA was the only therapy in 5 (17.2%) vs 5 (15.6%) patients in EG and NG. Other treatment for EG-RI included chemotherapy combined with ATRA in 19 (65.5%), where as in NG-RI only 6 (18.7%) received chemotherapy and ATRA. ATO was combined with ATRA in 4 (13.7%) of EG-RI and 19 (59.3%) of the NG-RI patients. Only 1 (3.4%) patient received ATRA, ATO and chemotherapy in EG-RI and 2 (6.2%) in NG-RI.Complications among the patients with RI in EG and NG were: DS and infection in 9 (31%) vs 9 (28.1%), DS only in 4 (13.7%) vs 6 (18.7%); infection only in 12 (41.3%) vs 9 (28.1%) respectively. There were 4 (13.7%) vs 8 (25%) in EG and NG which had neither infection nor DS. Among those with DS, steroids were used in 100% of the patients in both EG and NG. There were 11 (37.9%) vs 6 (18.7%) early deaths in patients with renal insufficiency in EG and NG.Conclusion: By our observation, RI is a frequent complication during induction in APL. Mortality in patients who develop RI tends to be high. Meticulous attention should be paid to kidney function during induction and the drugs should be appropriately dose reduced or held till resolution. [Display omitted] DisclosuresArellano:Cephalon Oncology: Research Funding. Kota:Pfizer: Consultancy; Novartis: Consultancy; Xcenda: Consultancy; Incyte: Consultancy; Leukemia Lymphoma Society: Research Funding; Takeda Pharmaceuticals: Consultancy.

A Prospective Multi-Center Trial Shows Reduction of Early Deaths (ED) and Improved Survival in Elderly Acute Promyelocytic Leukemia (APL) Patients (>60 years). Results of Using a Simplified Treatment Algorithm and Expert Support in Georgia, South Carolina and Neighboring States

Background: APL is the most curable leukemia with reported survival above 90% in many large co-operative group studies. These excellent outcomes are not seen in elderly patients where early deaths in trials are 10-18%. Population based registry data shows that ED rate in elderly APL patients is even higher with reported incidence of 24-50%. We conducted a prospective trial using a set of simplified treatment guidelines along with support from a dedicated team of APL experts. Herein, we report outcomes of patients >60 years treated within the prospective trial. We compared these to our institutional experience prior to implementation of the trial. Methods: The protocol consisted of a two page simplified treatment algorithm with emphasis on preventing bleeding, infection and differentiation syndrome (DS); the most common causes of ED. A network of Leukemia treatment centers was established by visiting most of the leukemia treatment centers in Georgia, South Carolina and neighboring states. Communication was established between the treating community oncologist and APL expert early in the diagnosis and was continued until the end of induction. Five other large leukemia treating centers in Georgia and South Carolina were part of the study and IRB approval was obtained. After 6 months of intense publicity, the study was implemented in 7/2013 and patients were prospectively accrued. Induction deaths of elderly APL patients in our study were compared to historical results at our institution (with IRB approval for retrospective review) prior to the initiation of this program. The study was funded by the Leukemia Lymphoma Society. Statistics are descriptive. Results: Between 1/2007 and 5/2016, we treated or co-managed a total of 70 patients above the age of 60 years. 23 were in the early group (EG) and 47 after 7/2013 in the new group (NG). Comparing the EG and NG patients, median age was 66 years (range 61-80) vs 69 (61-83 years), median WBC was 1.9 vs 2.3/mm3 (range 0.3-132 vs 0.3-38), male to female ratio was 1:2 and 1:1 respectively. Risk stratification based on WBC counts at presentation (> vs Conclusions: By our observation, elderly patients tolerate full doses of ATRA and ATO poorly during induction. ATRA/ATO at reduced doses is better tolerated and use of a simplified treatment algorithm with expert support has the potential to decrease induction mortality (13.3%) and improve population wide survival (77.8%) (1 year survival in patients >60 years based on Swedish Registry data ~ 37%) in elderly APL patients. Disclosures Kota:Leukemia Lymphoma Society: Research Funding; Ariad Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees; Incyte: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees. Heffner:Millennium: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding. Stuart:Bayer: Research Funding; Celator: Research Funding; Incyte: Research Funding; Agios: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Astellas: Research Funding. Gerber:Spectrum: Membership on an entity9s Board of Directors or advisory committees; Janssen: Research Funding; Alexion: Membership on an entity9s Board of Directors or advisory committees; Seattle Genetics: Membership on an entity9s Board of Directors or advisory committees. Grunwald:Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Ariad: Membership on an entity9s Board of Directors or advisory committees; Janssen: Research Funding; Alexion: Membership on an entity9s Board of Directors or advisory committees; Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Jillella:Leukemia Lymphoma Society: Research Funding.