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PurposeCombined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL) in an attempt to improve outcomes.Patients and methodsThree patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks, followed by oral AZT 250 mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART) with a second nucleoside reverse transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2 (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90 mg/kg bid were administered on days 1-14. One patient received anti-EpsteinBarr virus (EBV)-maintenance therapy with ganciclovir, followed by cidofovir [1].ResultsAll patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT) as second linetreatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histologically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable.ConclusionAlthough IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIVassociated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.

Background Data on benefit and toxicity by treatment intensification for AML are now available and allow rediscussing current dosing. Methods In a multicenter trial involving patients between 16 and 86 years of age, patients below 60 years received uniform double induction by the 1st course with standard dose araC/ daunorubicin (60mg/m²x3)/ thioguanine followed by the 2nd course with high-dose araC (3g/m²x6)/ mitoxantrone (10mg/m²x3), or randomly two high-dose courses. As age adaption patients of 60y or older received the 2nd course only in case of persistent blasts, and high-dose araC at 1 instead of 3g/m². Post remission treatment was consolidation and maintenance or randomly autologous stem cell transplantation in younger patients. Results 3369 patients entered the trial with 1843 patients 60y or older. A multivariate analysis identified age as continuous variable, favorable cytogenetics/ molecular genetics, unfavorable cytogenetics, white blood cell count and lactate dehydrogenase as categorical variables to be risk factors predicting complete remission, overall survival as well as relapse free survival. To separate the age effect from the treatment effect, two subgroups of similar age and baseline characteristics but different treatment were compared. Thus, the 239 patients aged 57-59 and the 336 patients aged 60-62 years shared not only similar age but also similar baseline characteristics, while their treatment by protocol and age adaption differed substantially. The difference as expressed by the cumulative araC dosis amounted to a factor of 3.6, which however did not translate into a different overall survival (equally 28%) or relapse rate (equally 70%) at 5 years. In contrast to different treatment, different age had a strong effect on outcome. Thus, the survival in patients aged 16-46y was 65% at 5 years versus 40% in those of 47-59y receiving the same treatment (p< 0.001). A corresponding age related difference was also found between the patients of 60-66y and those of 67-86y (p< 0.001) receiving the same age adapted treatment. As shown by others in patients of 18-60y doubling an intermediate cumulative dose of araC produced excessive toxicity without therapeutic benefit (Löwenberg B et al. NEJM 2011; 364: 1027-36), while high dose daunorubicin (90mg/m²) instead of standard dose (45mg/m²) improved the remission rate and survival in younger patients (Fernandez H et al. NEJM 2009; 361: 1249-59) and older patients of 60-65y (Löwenberg B et al. NEJM 2009; 361: 1235-48). No comparable data are available about daunorubicin 60mg/m² the standard in present study. Conclusion Age and disease biology rather than chemotherapy intensity are the main determinants of outcome in AML. Once a certain intensity and antileukemic effect has been achieved, a further escalation does not seem to overcome the age factor in AML. Present data require rediscussing current chemotherapy dosing and treatment alternatives. Disclosures: No relevant conflicts of interest to declare.

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1509 Introduction: Both, patients' age and genetic groups are important predictors of outcome in AML while their influence remains poorly quantified and compared. Methods: In the AMLCG (Acute Myeloid Leukemia Cooperative Group) 1999 trial 1470 patients (pts) were 16–59y and 1747 pts were 60–85y of age. 95% of pts could be classified according to genetic risk groups as standardized on behalf of the ELN (Blood 2010;115:453-74). Their treatment was randomized between TAD-HAM versus HAM-HAM induction (TAD, standard dose thioguanine, cytarabine, daunorubicin 60mg/m2 × 3; HAM, high-dose cytarabine 3g/m2 × 6, mitoxantrone 10mg/m2 × 3), TAD consolidation and monthly maintenance vs TAD and autologous SCT, any chemotherapy + vs – G-CSF priming. All assignment was done upfront. Pts of <60y received routine double induction and full dose HAM while pts of 60+y preferentially received only 1 course induction and HAM at 1g instead of 3g cytarabine/m2 × 6. Results: With little difference according to randomizations, pts <60y and 60+y achieved a complete remission (CR) rate of 65% and 51% (p<.001), a 5y overall survival (OS) of 41% and 14% (p<.001), and a 5y ongoing remission duration (RD) of 47% and 21% (p<.001). We particularly focussed on pts around 60y of age and compared the 231 pts of 57–59y with the 315 pts of 60–62y. Corresponding to their similar age the two groups showed similar baseline characteristics. In contrast and due to the cutoff point for age adaption at 60y they differed considerably in treatment. Expressed by the cumulative dosage of cytarabine in induction and early consolidation, the difference between the two groups was by factor 3.9. This difference, however, did not translate into a different outcome being 60% vs 57% CR (p=0.59), 28% vs 25% 5y OS (p=0.40) and 32% vs 29% RD at 5y (p=0.46). Through focussing on patients around 60y a relevant influence of chemotherapy intensity and age adaption could thus be excluded. A multivariable analysis in the complete patients between 16 and 85y of age identified genetic groups and age (as a continuous variable) to be the only risk factors predicting CR, OS as well as RD whereas other risk factors such as secondary AML, WBC, and LDH were predictive only for subsets of endpoints. Among all treatment variables only HAM-HAM induction was associated with a slightly superior RD (p= 0.0715). Grouping by age resulted in 4 age categories (16–46y:n=683, 47–59y: n=787, 60–66y: n=815, and 67+y: n=932) with significantly different OS as well as RD. Subdividing by genetic groups (favorable: n=593, intermediate I: n=1169, intermediate II: n=526, adverse: n=780) distinguished 3 significantly different categories (favorable, intermediate, adverse), a pattern observed in all age groups. Conclusion: In a defined representative population of pts with AML the longterm outcome was mainly determined by age and genetic groups but not by treatment intensity or variables, nor by other prognostic factors. Both, age and genetic groups should thus contribute to a reliable prediction of outcome in AML. Disclosures: No relevant conflicts of interest to declare.