Acute Leukemia and Myelodysplastic Syndrome: Outcomes in Patients with Chronic Lymphocytic Leukemia (CLL) At MD Anderson Cancer Center (MDACC)
Authors: Tambaro Francesco Paolo , Garcia-Manero Guillermo , Faderl Stefan , O'Brien Susan , Ferrajoli Alessandra , Burger Jan A. , Trinh Long Xuan , Lerner Susan , Kantarjian Hagop M. , Keating Michael J , Wierda William G. 
Published: October 2019

Abstract
Abstract 981
Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in patients (pts) with CLL and have mainly been attributed with exposure to chemotherapy and radiotherapy. In contrast, CLL is frequently associated with second solid malignancies. Associations between AL, MDS and CLL have rarely been reported and large series of outcomes for such patients are lacking; available literature typically consists of studies with fewer than 10 such pts.
We identified 95 pts (out of 8685 CLL pts) evaluated at MDACC between August ‘81 and August ‘10 who had a diagnosis (Dx) of CLL and were concurrently (n=5) or subsequently (n=90) diagnosed with AL (n=38) or MDS (n=57). The median age at CLL Dx was 60 (25–83) and at AL/MDS Dx 66 (41–85) yrs; 76% were male. The median follow up time from presentation to MDACC was 58 mo (7–191). There were 12 pts who had no prior CLL chemotherapy (Table). The median number of prior CLL chemotherapy regimens to AL and MDS Dx was 2 (0–9) and 1 (0–8), respectively. For pts who received 1 prior CLL treatment before transformation, 90% (34/38) received fludarabine-based therapy (26 FCR, 3 FC, 1 CFAR, 4 fludarabine monotherapy). The median times from CLL Dx to AL/MDS Dx, survival from CLL Dx, and overall survival from AL/MDS Dx are shown (Table). There currently are 11 living pts (AL n=4; MDS n=7), their median survival is 95 mo from CLL Dx and 27 mo from AL/MDS Dx. Seven pts underwent allogeneic stem cell transplant for AL/MDS, 3 are living.TablenPts with # Prior CLL TxMedian Time (mo)01≥2Time CLL Dx to AL/MDS DxSurvival from CLL DxSurvival from AL/MDS DxAL384142057655MDS578252467809.3
Of the 38 pts who developed AL, 33 were AML (FAB: 4 M0, 5 M1, 5 M2, 4 M4, 5 M5, 4 M6, 6 missing), 3 were ALL (1Ph+), 1 was biphenotypic, and 1 had extramedullary (bladder) AML. The median % bone marrow (BM) blasts at AL Dx was 40%; median WBC, HGB, and PLT were 5.1K/μl, 9.9 gm/dl, and 38K/μl, respectively. CLL was present in BM in 42% at AL Dx. Unfavorable AML karyotype was noted in 26 (68%) and intermediate-risk in 7 (18%) pts. CD7 was detected by flow cytometry in 6 AML pts. The median number of treatments for AL was 1 (0–4); 1 pt was untreated. The most common treatment was cytarabine-based (30 pts). Survival for pts with CD7 expression by AML blasts was 2 mo vs. 7 mo for pts without CD7 expression (p<.001). There was no association between # of prior CLL regimens, karyotype category, or presence of CLL at AL Dx and survival from AL.
In the 57 pts diagnosed with MDS, all IPSS were represented: 6 low-, 15 Int-1-, 25 Int-2-, 7 high-risk, and 4 missing. The median % BM blast was 3%; and median ANC, HGB, and PLT were 1.27K/μl, 9.8 gm/dl, and 53K/μl, respectively at MDS Dx. CLL was present in the BM in 49% at MDS diagnosis. MDS karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 pts (3 missing). The median number of treatments for MDS was 1(0–4); 9 pts were untreated. The most common treatments were hypomethylating agents (19 pts) and cytarabine-based regimens (11 pts). 10 pts with MDS subsequently transformed to AML; median time from MDS to AML transformation was 6.5 mo. Survival from MDS Dx was correlated with IPSS: 25 mo for low-, 10.2 mo for Int-1-, 6.7 mo for Int-2-, and 7.4 mo for high-risk (p=.003). In addition, pts who had no prior CLL chemotherapy had median survival of 37 mo vs. 9.7 mo for pts with 1 prior CLL treatment and 5.9 mo for those with ≥2 (p=.007). Pts who had favorable karyotype had superior survival (25 mo), compared to patients with intermediate (7 mo) or poor-risk (8 mo) karyotype (p=.002). There was no association between presence of CLL at MDS Dx and survival from MDS. Detailed analyses of prior CLL treatment and other risk factors for AL/MDS are ongoing as are comparisons of outcomes for pts with non-CLL associated secondary AL/MDS.
In conclusion, outcomes for pts with CLL who are subsequently diagnosed with AL or MDS are poor; AL/MDS may occur in the absence of CLL chemotherapy. In pts who received 1 prior CLL treatment, the most common regimen was purine analogue combined with alkylating agent±mAb. Outcomes for AL in CLL are similar to reports for secondary, poor prognosis ALs. Survival from MDS was correlated with IPSS, karyotype, # of prior CLL regimens. Risk factors for AL/MDS are being assessed. Effective therapies for these pts are desperately needed.

Disclosures:
No relevant conflicts of interest to declare.