1. Survival and Clinical Aspects for Patients with Chronic Lymphocytic Leukemia in Kermanshah, Iran
Mehrdad Payandeh
Department of Hematology and Oncology,
Kermanshah University of Medical Sciences, Kermanshah, Iran
August 18-19, 2016 London, UK

2. Faculty Medical Researcher Masoud Sadeghi, MSc Edris Sadeghi, MSc
Department of Hematologic Malignancies, Medical Oncology
Kermanshah University of Medical Sciences
Kermanshah, Iran
Masoud Sadeghi, MSc
This slide lists the faculty who were involved in the production of these slides.

3. Background
Chronic lymphocytic leukemia (CLL), most common leukemia in adults in Western countries but is relatively rare in Asia

4. Chronic Lymphocytic Leukemia
~ 15,000 new cases per yr
Most common adult leukemia
Chronic, incurable, mature B-cell neoplasm
Most pts present with asymptomatic increase in lymphocyte count
Many asymptomatic pts do not initially require therapy
Therapy required once symptoms, cytopenias, or large lymphadenopathy occur
Slide credit: clinicaloptions.com

5. CLL: Incidence of Genetic Lesions
Treatment naïve CLL[1]
(n = 452)
CLL8[2]
Frontline
FC vs FCR (n = 635)
CLL3X[3,4]
High-Risk
AlloSCT (n = 80)
CLL2H[5,6]
F-Refractory Alemtuzumab (n = 97)
TP53mut
5.3
11.5
30.0
39.0
NOTCH1mut
12.6
10.0
14.0
13.4
SF3B1mut
8.6
18.4
26.0
17.5
IGHV UM
32.8
63.0
96.0
79.0
del(17p)
8.4
18.1
30.1
del(11q)
16.0
24.6
36.1
19.4
F, fludarabine.
1. Puente XS, et al. Nature. 2015;526:
2. Stilgenbauer S, et al. Blood. 2014;123: Dreger P, et al. ASH Abstract Dreger P, et al. Blood. 2013;121: Schnaiter A, et al. Blood. 2013;122: Schneiter A, et al. ASH Abstract 710.
Slide credit: clinicaloptions.com

6. Estimate of OS According to Cytogenetics
Median OS, yrs NR
5.0
Events, n 27 53
41 57
Total, n 155
228 99
101
95% CI
Del(13q14) Normal/+12 NOTCH1 M/SF3B1 M/del(11q22-q23)
TP53 DIS/BIRC3 DIS
100 80 60
Del(13q14) vs normal/+12
Normal/+12 vs NOTCH1 M/SF3B1 M/del(11q22-q23)
NOTCH1 M/SF3B1 M/del(11q22-q23)
vs TP53 DIS/BIRC3 DIS
P = .0406
P = .0082
P = .0196
Cumulative Probability of OS (%) 40 20
P < .0001 5 10 15
Yrs From Diagnosis
Slide credit: clinicaloptions.com
Rossi D, et al. Blood. 2013;121:

7. Critical Signaling Pathways and New Targeted Agents in B-Cell Malignancies
BCR signaling is required for tumor expansion and proliferation
BCR signaling up-regulated in CLL
New inhibitors are targeting multiple components of BCR signaling including PI3K delta, BTK, and Syk
BCR
LYN
SYK
Idelalisib
Duvelisib
Pilaralisib ┬
BCR, B-cell antigen receptor; BTK, Bruton’s tyrosine kinase; GSK-3, glycogen synthase kinase 3; mTOR, mammalian target of rapamycin; NF-kβ, nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K, phosphatidylinositide 3-kinases; PKC, protein kinase C; PLC, phospholipase C; Syk, spleen tyrosine kinase. ┬
PI3K
delta
Ibrutinib
BTK
PLCγ2
AKT
GSK-3
NF-kβ
pathway ┬
PKC
mTOR
Everolimus
p70s6k
elf4E
Slide credit: clinicaloptions.com

8. Frontline CLL Therapy in 2016
Clinical trial should be considered for all pts with CLL
Population
Initial Therapy
Younger, fit pts
FCR (especially mutated IGHV)
Older pts with comorbidities
Bendamustine/Rituximab
Chlorambucil/Obinutuzumab
Chlorambucil/Ofatumumab
Ibrutinib
Pts with del(17p) or
TP53 mutation
AlloSCT?
Slide credit: clinicaloptions.com

9. CLL Therapy in the Future
Clinical trial should be considered for all pts with CLL
Population
Initial Therapy
Relapsed Therapy
Younger, fit pts with low risk
FCR (especially mutated IGHV)
Ibrutinib
Idelalisib + R
Ibrutinib + BR*
Idelalisib + BR*
Venetoclax*
Older pts with comorbidities
Bendamustine/rituximab
Chlorambucil/obinutuzumab
Chlorambucil/ofatumumab
Pts with del(17p)
or TP53 mutation
AlloSCT?
Venetoclax
*Not currently approved by the FDA.
Slide credit: clinicaloptions.com

10. Materials and Methods
In this study, we did a retrospective analysis from 109 CLL patients that referred to Clinic of Hematology- Oncology, Kermanshah, Iran, between January 2006 and March 2014.

11. Materials and Methods
For all of patients were calculated sex, age, survival, AIHA, Evan’s syndrome, lymphadenopathy, organomegaly, B symptoms, white blood cell, hemoglobin and platelet by patient or pathology reports or laboratory tests.

12. Materials and Methods
Overall survival (OS) was calculated as the time from diagnosis to death or last contact.
Curve of OS was plotted by Kaplan- Meier plot in Graph Pad prism 5 Software in a five-year period (March March 2014) with completing a two-year period and curves of OS for male and female were compared by log-rank test.

13. Table 1. The baseline characteristics in the patients at time of diagnosis of chronic lymphocytic leukemia (n=109)

14. Patients Results
Of all patients, 22 patients (20.8%) were treated with IVIG and 46 patients (43.3%) were treated with vaccine of the Flu.

15. Patients Results
Of 109 patients with CLL, 29 patients died and 23 patients were lost to follow-up before completing a two-year period and should therefore be excluded from the analysis.

16. Table 2. The Primary Clinical Variables in CLL Patients

17. Table 3. Mean age and Percentage of Male for Chronic Lymphocytic Leukemia in Asian Countries

18. Table 4. Mean overall survival and survival rate (5- year period) for chronic lymphocytic leukemia in Asian countries

19. Treatment Results
Survival rate for patients was 64% and mean of overall survival for 5-year period was 38.5 months.

20. Treatment Results
There is a significant difference between sex and OS rate (P=0.018, 95% CI of ratio , Hazard Ratio (HR) 2.31).The survival rate for females is 78% and for males is 53.5%.

21. Figure 1. The 5-year overall survival for chronic lymphocytic leukemia for all of patients

22. Figure 2. The 5-year overall survival rate for chronic lymphocytic leukemia by sex

23. Therefore, it is probably that life conditions (smoking, ,hard work, etc) in males comparing with females have more affect on the appearance and mortality of CLL.
In Western Iran (Kermanshah) majority of males work more than females in hard condition and smoking in males is more.

24. In previous studies were reported that smoking (Muirhead et al
In previous studies were reported that smoking (Muirhead et al., 2009) and quality of life (Shanafelt et al., 2009) influence on development of CLL.

25. Conclusion
First of all, CLL is a rare case of malignancy in Asian countries and lymphadenopathy and organomegaly, immunodeficiencies and the Flu virus are the main complaints in CLL.
Second, in these countries, CLL is more in males and in ages of above 60 years.
Third, here is not relationship between sex and age in patients.
At last, OS rate in females is higher than males.

26. Thank You For Your Attention