Litzow, Mark R.

Summary Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37–144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11·7% underwent autologous and 40·6% allogeneic transplant, while in CR1. Of the autologous patients, 43·2% relapsed early and 3·4% relapsed late. However, among the allogeneic patients, 13·2% relapsed early and only 1·3% late. The five‐year overall survival from relapse was 5·8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.

Abstract There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.

e18549 Background: Many vitamin deficiencies can cause anemia. It is prudent prior to diagnosing a myeloid neoplasm, to check for vitamin deficiencies and correct them. Myelodysplastic syndromes with ring sideroblasts (MDS-RS) are associated with anemia. Pyridoxine (Vit B6) replacement may improve anemia found in sideroblastic anemia. The study was to determine how frequently Vit B6 was assessed, replaced and impact replacement had on outcomes in MDS-RS. Methods: Study subjects were from the Mayo Clinic Myelodysplastic syndrome (MDS) database which contains 1315 patients (pts). Appropriate IRB approval was obtained. Diagnosis of MDS and its sub-classification was done according to World Health Organization 2016 criteria. A response was any improvement in hemoglobin. Overall survival (OS) estimates were calculated using Kaplan-Meier curves and univariate and multivariate analysis was done using JMP software version 13. Results: Among 1315 pts with MDS, 161 pts had a diagnosis of MDS-RS. Median age was 73, and 55 (34%) pts were females. Thirty-nine (36%) pts had very low, 53 (50%) low, 9 (8%) intermediate, 3 (3%) high, and 2 (1%) had very high revised international prognostic score. The median white blood cell count was 5.4 x109, platelet count was 255 x109, and hemoglobin was 9.9 gm/dL. Five pts (3%) had a Vit B6 levels done; out of whom, 4 (80%) were not Vit B6 deficient. Among 42 (26%) pts who had Vit B6 replacement, 21 (50%) had no response, 4 (10%) had a response and 17 (40%) had unknown response. 103 (64%) of the pts were transfusion independent (TI). Overall survival in pts who are transfusion dependent was 68 months compared to 85 in pts who are TI (Wilcoxon P =.03). There was an improvement in OS in the group that had Vit B6 replacement compared to the group with no Vit B6 replacement (92 months vs 68 months, Wilcoxon P =.07). Response to Vit B6 replacement did not show OS benefit. Acute Leukemia transformation in Vit B6 replacement was 2% and 6% in pts. who did not have Vit B6 replacement (P= .4). Conclusions: Vit B6 was not checked often in MDS-RS pts. There was a borderline improvement in OS in Vit B6 replacement group (p= .07). Response did not affect OS. A larger prospective study is needed to study Vit B6 role in MDS-RS.

7053 Background: The revised International Prognostic Scoring System (IPSS-R) aids in prognosticating MDS. The percentage (%) of blasts in the bone marrow is one of the major determinants of the scoring system. The aspirate blast % is utilized as the standard of care, but there could be discrepancies in the blast % reported by the aspirate and the biopsy. We aim to study the possible use of bone marrow biopsy blasts in MDS-EB in calculating IPSS-R. Methods: The MDS database was reviewed for cases of MDS-EB after due IRB approval. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and biopsy blast % (IPSS-RBx). The biopsy blast % was reported morphologically or by the CD34 stain. Whenever a range was reported the highest value was utilized as the blast %. Suboptimal aspirates were excluded from the study. The overall survival (OS) was determined by IPSS-RAsp, IPSS-RBx and IPSS-R highest blast (IPSS-RHi). OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno’s concordance statistic was used to compare all 3 risk scoring systems. Results: Of 1322 patients, 431 (33%) cases were identified with MDS-EB; out of which 173 cases had both blasts reported in the biopsy and the aspirate. Out of 173 cases, 35 (20%) had MDS-EB1, and 61 (35%) had MDS EB-2 based on both biopsy and aspirate (concordant cases). Seventy seven (45%) patients changed from EB-1 to EB2 or vice versa based on the biopsy blast (44/77 (57%) cases were upstaged). The OS outcomes based on the IPSS-RBx biopsy showed a clear and meaningful separation with median OS decreasing with increased risk but IPSS-RAsp and IPSS-RHi did not (Table). We compared the 3 models for observed OS differences using the Uno model and there was no statistically significant difference. Conclusions: IPSS-RBx (but not IPSS-RAsp and IPSS-RHi) identified prognostic groups for OS with median OS decreasing with increased risk. The small sample size may have led to an insignificant effect on model power by Uno model. This finding needs to be validated by other centers. [Table: see text]

7094 Background: Obesity is associated with comorbidities that could cause negative outcome upon delivering intensive care. In pediatric AML patients (pts), obesity was associated with more toxicity and worse prognosis. Here, we study Body-Mass Index (BMI) impact on clinical outcome of adult AML pts. Methods: A total of 180 adult pts with AML between 2003-2011 were enrolled. Retrospective data included demographics, labs, cytogenetics and outcome. LeukemiaNET Standardization (LNS), complete remission (CR), overall survival (OS) and relapse free survival (RFS) were obtained (Dohner E, Blood 2010). BMI of 25-30 was defined as overweight, while >30 as obesity. Fischer’s and Wilcoxon tests were used for comparatives between groups, cox proportional hazards and logistic regression for associations for OS/RFS and CR, Kaplan-Meier test for OS and RFS estimates via JMP software V9.0. IRB approval was obtained according to Helsinki declaration. Results: The median age was 63 years, with 115 (64%) were men. Of 159 pts, karyotype was favorable, Intermediate I, II and adverse in 21 (13%), 76 (48%), 23 (%14) and 39 (25%) pts respectively. Median BMI was 28.2 (range 16.8-47.8). 48 (26%) had normal BMI, 62 (34%) were overweight, and 70 (38%) were obese. At diagnosis, BMI classes were not associated with age, sex, glucose, white blood count (WBC), platelets, blasts, ECOG status, LNS, FLT3/NPM1 status; nor treatment toxicities, CR rates, or relapse after CR. BMI classes were associated with presence of concomitant comorbidities (p=0.047) and glucose levels (p=0.044). In univariate analysis, overweight (OR=1.8, p=0.16) and obesity (OR=1.9, p=0.13) did not affect CR rates. On adjusting for age, sex, LNS, WBC and blast count at diagnosis, only overweight pts had a significant higher CR (76% vs 63%) rates (OR=2.99, p=0.043). OS and RFS were not associated with BMI in univariate (p=0.51) and multivariate (p=0.32) models. Median OS and RFS were not different across BMI subgroups (p=0.52 and 0.59). Conclusions: BMI subgroups showed no correlation with treatment toxicity, LNS, relapse rates, OS or RFS. This should encourage giving therapy to pts regardless of their BMI status. Overweight was associated with better CR rates despite increased concomitant morbidities.

7064 Background: Obesity is a growing medical challenge that has strong association with many comorbid diseases. Body mass index (BMI) is used as one indicator for obesity. A few papers have linked hematological cancers with a worse prognosis if obesity was present. Aim: to study the influence of obesity clinical outcome in patients (pts) with CMML. Methods: A retrospective chart review of pts with CMML at Mayo Clinic Rochester between 1994–2011 was done. BMI was calculated at diagnosis or first time visit. Overweight was defined as BMI ≥25, while obesity as BMI >30. IRB approval was obtained. Comparison between medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier estimates via JMP software v.9. Results: We found227 pts with a median follow-up of 311 days, 68% of which weremales. Median age was 71 years, hemoglobin 11 gm/dL, white blood cells (WBC) 12x 109/L, and platelets 90x 109/L. Obese pts had a median age of 68 (p=0.0058), hemoglobin 11 gm/dL (p=0.0018), WBC 13.5 x 109/L, platelets 115x109/L (p=0.012), PB blasts 0, bone marrow (BM) blasts 3.5% compared to non-obese pts (73, 10, 11, 78, 0, 3%, respectively). Diploid cytogenetics were similar in both groups (68% vs 64%, respectively, p=0.54). Leukemic transformation into acute myeloid leukemia (LT) was found in 13% vs 10% (p=0.83). Overall response (OR) was 24% and 23%, respectively (p=0.2), when limited to hypomethylating agents OR was 33% vs 27%, respectively (p=0.62). Median OS was found to be similar (571 day vs 569 days, respectively, p=0.56). When compared, overweight pts had similar outcome to non-overweight. Median LT was 11% vs 15% respectively, OR was 21% vs 28% respectively (p=0.5), and OS was 571 days vs 549 days respectively (p=0.21). On a multivariate analysis age, hemoglobin, platelets, BM blasts%, gender, and obesity (p=0.048) were of a significant value for OS. Conclusions: When compared, both obesity and overweight did not affect demographic characteristics, overall response, or transformation into AML. When comparing median overall survival, obesity was not a significant factor, possibly due to short follow-up. However, on multivariate analysis obesity did have a negative impact on overall survival.

6614 Background: CDKN2A locus on chromosome 9p21 is implicated in altered molecular pathways leading to leukemogenesis as a tumor suppressor by inhibiting the proliferative kinases CDK4/CDK6 and blocking the cell-cycle division during G1/S phase. Deletion of CDKN2A locus is frequently seen in ALL, although prognostic significance remains unclear. Methods: Retrospective chart review at Mayo Clinic between 8/2005-11/2011 was performed on adult B-ALL patients (pts) who underwent fluorescent in situ hybridization (FISH) studies at diagnosis. Survival estimate was calculated using Kaplan-Meier statistics. Event-free survival (EFS) was defined as time between diagnosis and induction failure, relapse, or death, while overall survival (OS) as time between diagnosis and death Results: Out of 27 pts who had FISH studies for CDKN2A, 15 (56%) pts had CDKN2A deletions (8 homozygous/7 hemizygous), while 12 (44%) pts had diploid cytogenetics (none had abnormalities of MLL, bcr/abl fusion or CDKN2A deletion on FISH). There was no significant difference in median age, gender, WBC, hemoglobin, platelet count, LDH or complete remission (CR) rate (p=0.924) between the two groups. CDKN2A-deleted pts had higher circulating blasts (34% vs 16%, p=0.017). Of 13 CDKN2A-deleted pts, chromosome 9p was intact in 9 (69%) pts using routine cytogenetics. In the CDKN2A-deleted group, allogeneic stem cell transplant (ASCT) was performed in 7 (47%) pts at first CR and 1 at second CR. Four of 15 (27%) CDKN2A-deleted pts also had bcr/abl fusion. Five-year EFS was poorer in CDKN2A-deleted pts compared to normal FISH group (22% vs 60%, p=0.042), while 5-year OS was 72% vs 60% (p=0.308), respectively. Excluding the 4 bcr/abl fusion pts, 5-year EFS was still statistically significant (p=0.008). In the CDKN2A deleted group, both 5-yr EFS (80% vs 0%, p=0.006) and OS (100% vs 42%, p=0.016) were significantly superior in pts who received ASCT. Conclusions: CDKN2A deletions predict earlier relapse in pts with B-ALL. Majority of 9p abnormalities were only found by FISH testing and missed by conventional cytogenetics. In CDKN2A deleted pts, ASCT gave overall survival advantage. Further investigation through larger cohorts of pts is needed to validate these findings.

7605 Background: In the setting of autologous stem cell transplantation (ASCT) in multiple myeloma (MM), it has been shown that peripheral blood absolute lymphocyte count (ALC) on day 15 is an independent prognostic factor for clinical outcomes. Recently the International Staging System (ISS) for MM has been developed as a simple staging system to assess survival in newly diagnosed MM patients. The role of ALC on survival in newly diagnosed MM patients is unknown. Methods: Between 1994 and 2002, 1,835 consecutive MM patients were evaluated at the Mayo Clinic, Rochester. Of these patients, we retrospectively analyzed 584 MM patients that were originally diagnosed and followed at the Mayo Clinic. The primary end point was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). OS was measured from the date of diagnosis to time of death or last follow-up. ALC was analyzed as a continuous variable and dichotomized based on finding the optimal cut point based on the log-rank statistic. ALC was then compared to the ISS. Results: The median age of the cohort was 67 years (range: 29–94 years), including 234 females and 350 males. The median follow-up was 32 months (range: 1–136 months). The median ALC at diagnosis was 1.2 x 109/L (range: 0.12–5.44 x 109/L). ALC, as a continuos variables was identified as a prognostic factor for OS (HR= 0.466, 95%CI= 0.396–0.547, p < 0.0001). MM patients with an ALC ≥ 1.3 x 109/L experienced a superior OS compared with MM patients with an ALC < 1.3 x 109/L (55.5 months versus 22.6 months, p< 0.0001). In the multivariate analysis, ALC was independent prognostic factor when compared to the ISS (HR = 0.580, 95%CI=0.518–0.647, p< 0.0001). Conclusions: Our study shows that ALC at diagnosis for MM is an independent prognostic factor for OS, suggesting how the host immune status plays a critical role in the survival of patients with MM. No significant financial relationships to disclose.

8118 Background: Autologous stem cell transplantation (ASCT) improves survival and remains the standard of care for patients with newly diagnosed myeloma considered eligible for transplant. However, ASCT is not curative and patients relapse after a median interval of 24–30 months. While new therapeutic options have become available for relapsed MM, repeat ASCT remains an option especially when previously collected stem cells are available. The outcome of pts going to a second SCT in the relapsed setting has not been studied extensively. Methods: We identified pts with myeloma who received a second SCT from a prospectively maintained database. Planned tandem ASCTs were excluded. 56 pts received a second SCT for relapsed MM, including 11 allogeneic SCTs. Among the 45 second ASCTs, 5 were followed by reduced intensity allogeneic SCT and were analyzed with the allogeneic group. Results: The median age at second ASCT was 60.2 yrs (range, 41.3–74.4) and 27 (68%) were males. The median time to second ASCT from diagnosis, first ASCT and relapse were 47.4 mos (22.8–158.6), 36.3 mos (13.5–129.8) and 7.2 mos (1–32) respectively. Among patients receiving second APBSC, 14 (35%) patients were alive with a median follow up of 10.5 mos (1–45 mos). All patients received melphalan conditioning. The median time to neutrophil engraftment was 15 days and platelet engraftment was 16 days. The median hospitalization was 4 days (range 0–33) and there was one transplant related death in the group. The best response included 13 pts with CR (33%), 4 with VGPR (10%), and 19 with PR (48%). MM has relapsed in 22 (55%) pts with a median PFS of 12.5 mos from second ASCT. The median estimated OS from diagnosis, first ASCT and second ASCT were 100.5 mos, 65.9 mos, and 30.6 mos respectively. Among the 16 pts receiving allogeneic SCT, 8 pts (50%) were alive at analysis with a median PFS and OS from transplant of 17.9 mos and 33.5 mos respectively. Conclusions: Second ASCT as salvage therapy for relapsed MM is a viable approach and has a favorable outcome in this selected group of patients. The toxicity, engraftment kinetics, hospitalization and the response rates are comparable to patients undergoing initial ASCT. Allogeneic SCT with or with out a preceding ASCT results in comparable survival in selected patients with high risk disease. No significant financial relationships to disclose.