This document summarizes a study that evaluated the prognostic impact of the human Chitinase 3-like 1 (CHI3L1) biomarker in adult patients with acute myeloid leukemia (AML). The study found that high initial levels of CHI3L1 correlated with worse overall survival and disease-free survival in AML patients. While high CHI3L1 levels did not predict response to induction chemotherapy, normalization of initially high levels after treatment was associated with better response. The study concludes that CHI3L1 shows potential as a prognostic biomarker for outcomes in AML patients.

1. Prognostic impact of Human
Chitinase 3-like 1 in adult Acute
Myeloid Leukemia
By
Ahmad Yusuf Mohammad Badawy
MB BCh, Zagazig .
Under Supervision Of:
Prof. Dr. Fouad Mohammad Abu-Taleb
Prof. and head of medical oncology& hematology dept,
Zagazig University.
Dr. Asmaa Hosni El Esh
Assistant Prof. of clinical Pathology,
Zagazig University.
Dr. Ashraf M. El Hefni
Assistant Prof. of Hematology
Zagazig University

2. Introduction
• Acute myeloid leukemia (AML) is a
malignant disorder of the blood
characterized by impaired differentiation
and proliferation of hematopoietic
precursor cells, resulting in abnormal
accumulation of immature precursors and
suppression of growth and maturation of
cells involved in normal hematopoiesis
(Russell et al. 1997)

3. Introduction
• The prognosis for AML patients is variable,
ranging from survival of a few days to cure.
Clinical outcome can be partly predicted by
age, cytogenetic findings, and serum lactate
dehydrogenase at the time of diagnosis.
• It is important to identify new biomarkers in
AML patients for the prediction of prognosis
and treatment response, detection of relapse,
and monitoring for minimal residual disease
of AML. (Estey et al. 2001)

4. Introduction
• Human Chitinase 3-like-1(CHI3L1) is secreted
by cancer cells, macrophages, and neutrophils. It
may be a growth or differentiation factor, play
role in angiogenesis or protect against apoptosis
Interestingly, the studies showed that high
serum YKL-40 was related to short recurrence-
free interval and short overall survival in many
malignant diseases and that high serum YKL-40
was an independent prognostic variable of poor
prognosis (Ling H et al 2004)

5. Aim of the work
• This study aimed to evaluate role of human
Chitinase 3-like 1 in adult patients with acute
myeloid leukemia and its relation to other
prognostic factors.

6. Patients and methods
• This study had been carried out at
Hematology and Medical Oncology Unit,
Internal Medicine Department, Zagazig
University Hospital during the period
between February 2011 to February 2012. It
included 43 denovo AML patients and 10
healthy volunteers.

7. Patients and methods
All patients were subjected to:
• Complete Clinical History and Physical Examination.
• Routine Laboratory investigations:
▫ CBC, LFT, KFT, Serum electrolytes .i.e. Na+, K+, H+, Ca++, Po4
▫ PT, PTT and INR.
▫ E.S.R, LDH
▫ Virology: HBs Ag, HCV Ab, HIV Ab.
▫ Bone Marrow Aspiration, Immuno-Phenotyping, Cytogenetic
study.
• Routine radiology:
▫ Chest X-ray and CT chest if indicated.
▫ Pelvi-abdominal U/S and CT abdomen& pelvis if indicated.
▫ (E.C.G) and echocardiography.
• Special Laboratory investigation:
▫ plasma levels of Human Chitinase 3-like 1 will be assessed
before and after induction chemotherapy Plasma
concentrations of YKL-40 were determined by ELISA

8. Patients and methods
• All these patients were treated by induction 3&7
chemotherapy protocol
• BM aspirate evaluation was carried out at day
14 of end of induction protocol.
• Complete Remission (CR):
▫ normal cellularity of the BM after regeneration
with <5% blast cells
▫ The peripheral blood recovered completely
▫ No extra-medullary leukemic infiltrates were
present.
• Failure to attain CR will be consistent with
Failure or Non-Response (NR).

9. Results
%No.Character
10043
Age(in years):
Range(18-77)
Median (37)
46.5
53.5
20
23
Sex:
Male
Female
2
43
50
7
34
2
2
7
4.5
2
1
18
21
3
15
1
1
3
2
1
Clinical presentation:
CNS infiltration
Pallor,weakness,fatigue
Fever
Gum hypertrophy
Purpura, bleeding
Lymphadenopathy
Spleenomegaly
Hepatomegaly
Chloroma
Tumour lysis syndrome, renal
impairment
Table 1:Patient characteristics

10. Results
21
0
79
9
0
34
Virology:
Hcv Ab +ve
HBsAg +ve
Hcv/Hbv –ve
10043
Bone Marrow (B.M) Blasts (%):
Range (22-95)
X ±SD(70.55±20.85)
10043Immunophenotyping: +ve myeloid markers
16.3
41.9
30.2
11.6
7
18
13
5
FAB classification:
M1
M2
M4
M5
16.3
58.1
11.6
14
7
25
5
6
Cytogenetic study:
unfavorable
intermediate
favorable
Unknown

11. Results
high
normal
ykl40
Figure (1 ) showing YKL-40 level in study group
Plasma YKL40 was high in 35 cases (81.4%) while it was normal
in only 8 cases (18.6%) of the study group.

12. Results
Table (2) Independent sample t test
Comparing between YKL-40 levels in
AML cases vs control:
Mean ± S.D T P value
YKL-40
cases
5739.7 ± 6186.2 5.53 <0.001
YKL-40
control
466.7 ± 477.5

13. Results
Table (3) paired sample t test
Comparing between YKL-40 levels in
AML cases before and after induction
chemotherapy:
Mean ± S.D T P value
YKL-40 before
chemotherapy
5739.7 ± 6186.2
2.21 0.032YKL-40 after
chemotherapy
4011.7 ± 6236.7

14. Results
Table (4) Paired sample t test comparing
between YKL-40 levels in AML cases before and
after induction chemotherapy in responders
and non-responders:
Remission Mean ± S.D t P value
Achieved
(21) case
YKL-40 before
chemotherapy
4864.6 ±
6177.2
3.34 0.003YKL-40 after
chemotherapy
1077.9±1761.1
Not achieved
(22) case
YKL-40 before
chemotherapy
6575 ± 6236.7
-.258 0.799YKL-40 after
chemotherapy
6812±7616.9

15. Results
Table (5) showing Independent sample (t) test
comparing between plasma YKL-40 levels
before induction chemotherapy in responders
and non-responders:
Mean ± S.D T P value
YKL-40 before
chemotherapy in
responders (CR)
4864.57 ±
6177.2
-0.905 0.37
YKL-40 before
chemotherapy in
NON-responders (CR)
6575± 6220.7

16. Results
Table (6) Chi square Comparing between plasma
YKL-40 level with sex, FAB classification,
cytogenetic study and response to treatment:
PΧ2
High plasma YKL-
40
No %
Normal plasma
YKL-40
No. %
0.441.0115
20
5
3
Male
Female
0.95
9
0.36 13.9
15 34.8
10 23
4 9.3
1 2
3 6.9
3 6.9
1 2.3
FAB:
M1
M2
M4
M5
0.5522.17 16.2
19 44.1
4 9.3
5 11.6
0 0
6 13.9
1 2.3
1 2.3
Cytogenetic:
Unfavorable
Intermediate
Favorable
Unknown
0.0215.814 32.5
21 48.8
7 16.2
1 2.3
Response:
CR
NR

17. Results
Table (7) bivariate Spearman correlation
analysis test between plasma YKL-40 and age,
LDH level, and ESR, TLC, and BM blasts
Age TLC LDH ESR
BM
Blast
YKL40.befor
chemotherap
y
Correlation
Coefficient
.064 .222 .152 .195 .253
Sig. (2-tailed) .685 .152 .330 .210 .102
N 43 43 43 43 43

18. Results
Hb PLT Cr SGPT SGOT PT OS
YKL40.before
therapy
Correlation
Coefficient
-.347 -.165 .236 -.044 .184 .299 -.154
Sig. (2-tailed .023 .290 .127 .782 .238 .051 .323
Table (8) bivariate Spearman correlation
analysis test between plasma YKL-40 and Hb,
SGPT, SGOT, Creatinine level, PLT count and
overall survival

19. Results
Table(9): comparison between overall
survival and initial plasma YKL-40 before
therapy:
P valueLog
rank
High YKL-40
No. %
Normal YKL-40
No. %
0.034.369
16 477 89Censored
19 531 11Event
7.181 ± 0.918.75 ± 1.378Mean survival
±SD
5.390 –
8.965
6.049 – 11.45195%
confidence
interval

20. Results
Figure (II): comparison between overall survival
and initial plasma YKL-40 before therapy:

21. Results
• Table(10): comparison between disease
free survival and initial plasma YKL-40
before therapy:
P
value
Log
rank
High YKL-40
No. %
Normal YKL-40
No. %
0.034.694
10 28.57 75Censored
25 71.51 25Event
4.3 ± 0.9017.625 ± 1.457Mean survival
±SD
5.190–6.0654.76 – 10.48195% confidence
interval

22. Results
Figure (III): comparison between DFS and YKL-40
before therapy:

23. Results
• Table(11comparison between overall
survival and response to treatment:
P value
Log
rank
NR
No. %
CR
No. %
0.00110.650
8 36.415 71.4Censored
14 63.66 28.6Event
5.074 ± 1.210 ± 0.872Mean survival
± SD
2.720 – 7.4298.326-11.74595 %
confidence
interval

24. Results
Figure (IV): comparison between overall survival
and response to treatment

25. Conclusion
• Plasma YKL-40 can be a marker for predicting
outcome and survival in AML leukemia patients
• High initial YKL-40 is not a predictor for early
achievement of remission in AML.
• Normalization of initially high plasma YKL-40 is an
important sign of response.
• Plasma YKL-40 is an independent risk factor in
AML not related to other risk factors.
• Plasma YKL-40 is neither specific nor sensitive for
AML or other malignancies so cannot be used as a
marker for diagnosis.

26. Recommendations
• More studies are strongly needed to investigate
the function of YKL-40 in AML and bacterial
infections.