The Negative Correlation Between Diabetes

Mellitus and Acute Leukemia in Adults: Results

of a Large Retrospective Study Performed at
Two Major Tertiary Care Centers in Saudi Arabia
1Al-Anazi KA, 2Al-Jasser AM, 2Evans DAP, 2Shafi T,
1Aljurf MD, 1Al-Mohareb FI, 1Sahovic E, 1Al-Omar H, 1Al-Zahrani HA, 1Chaudhri NA, Al-Sharif FZ
1Section of Adult Hematology and Hematopoietic Stem Cell Transplant, King Faisal Cancer Centre,
King Faisal Specialist Hospital and Research Centre, P.O. Box: 3345, Riyadh 11211, Saudi Arabia.
2Departments of Pathology and Medicine, Armed Forces Hospital,

P.O. Box: 7897, Riyadh 11159, Saudi Arabia.

ABSTRACT complications, mortality and extramedullary disease, but a lower

Background: Despite the worldwide dramatic increase in
the prevalence of diabetes mellitus, the association between
this disease and acute leukemia has not been well explored.
Methods and Materials: A retrospective study of diabetes
mellitus in patients with acute leukemia was conducted at
Riyadh Armed Forces Hospital between January 1991 and
December 2002 and then the study was continued at King
Faisal Specialist Hospital and Research Centre in Riyadh
between January 2004 and December 2006.
Results: Out of 408 adults with acute leukemia treated at
both institutions, only 7 patients had diabetes mellitus at the
presentation of leukemia. The incidence of diabetes in adults
with acute leukemia in the Saudi population was 1.72% which
was extremely low in comparison with that of diabetes in adult
Saudis. All the study patients had type 2 diabetes and were
mostly obese or overweight. Compared to the control group of
patients, the study patients developed leukemia at an older age
with acute myeloid leukemia being the predominant type
encountered. The study group also had higher rates of infectious
relapse rate. Interestingly, both groups of patients had similar
rates of chromosomal abnormalities.
Conclusions: The study showed a clear negative association
between diabetes mellitus and acute leukemia in the adult Saudi
population. A possible explanation of this finding is that adult
patients with diabetes may have genes that have protective
effects against the development of acute leukemia.
INTRODUCTION
Diabetes mellitus (DM) has already reached epidemic
proportions in many populations.1-5 The rate of increase in
the prevalence of DM in the developing countries is
alarming. By the year 2025, more than three quarters of all
individuals with DM will reside in developing countries
according to the current estimates.1-3 India and China are
leading in the surge in DM, while Sub-Saharan Africa has
the lowest prevalence rate of DM.2 The prevalence of DM
for all age-groups world-wide has been estimated to be 2.8%
in the year 2000 and 4.4% in the year 2030.6 The epidemic
of DM is likely to continue even if levels of obesity remain
constant.6

The dietary shifts towards westernized food in many

Keywords: Diabetes mellitus: DM; acute leukemia: AL; countries in Asia, Africa and South America and the
hematopoietic stem cell transplant: HSCT; acute lymphoblastic sedentary life styles are the main predisposing factors for
leukemia: ALL; acute myeloid leukemia: AML. the development of: type 2 DM, obesity and other chronic
Correspondence to: Khalid Ahmed Al-Anazi, Associate Consultant, Section of Adult Hematology and Hematopoietic Stem Cell Transplant,
King Faisal Cancer Centre, King Faisal Specialist Hospital and Research Centre, P.O. Box: 3345, Riyadh 11211, Saudi Arabia.
33
Tel: 966 - 01 - 4568477, Fax: 966 - 01 - 4568477, E-mail: kaa_alanazi@yahoo.com
Khalid Ahmed Al-Anazi
disorders.5, 7, 8 The other environmental factors that
contribute to the disease are: age, hypertension,
dyslipidemia and gestational DM.9 Type 2 DM is caused by
a complicated interplay of genes. Obesity, sedentary work
and other lifestyle factors may be particularly strong in
releasing the genetic elements that cause this type of DM.9
The study described below was initiated by observing that
despite the fact that type 2 DM is a common health problem
and that acute leukemia (AL) is a rather common
malignancy in the adult Saudi population, the possibility of
having both existing in the same patient was extremely
low.
Methods and Materials
Riyadh Armed Forces Hospital (RAFH) and King Faisal
Specialist Hospital and Research Centre (KFSH&RC) in
Riyadh are major tertiary care centers with specialty services
including: intensive care, hematology/oncology and solid
organ as well as hematopoietic stem sell transplantation
(HSCT). A retrospective study of DM in patients with
acute leukemia (AL) was initially conducted at the
hematology ward and the HSCT unit at RAFH between
January 1991 and December 2002 then the same study
was continued at the leukemia and the HSCT units at
KFSH & RC in Riyadh between January 2004 and
December 2006. The records of patients with AL having
DM at the time of presentation of leukemia (study group)
were reviewed. Their results were compared to those of a
control group composed of patients with similar
backgrounds but never had DM at the presentation of their
AL. Only Saudi patients were included in the study so as
to have a homogenous population of patients. Very few
non-Saudi patients having DM and AL were excluded.
Patients having therapy-induced DM eg steroid induced
DM caused by treatment of acute lymphoblastic leukemia
(ALL) or graft versus host disease (GVHD) were also
excluded. The new diagnostic criteria for DM and impaired
fasting glucose adopted by the world health organization
(WHO) in the year 1999 were taken into consideration
throughout the two study periods.
STUDY PATIENTS
The study group consisted of 7 patients with AL. These
patients had DM at the time of AL presentation. Out of
the 7 study patients, there were 4 males and 3 females and
their ages ranged between 24 and 67 years with a median
age of 45 years. Five patients had acute myeloid leukemia
(AML), 1 had ALL and 1 had acute biphenotypic leukemia
(ABL). During hospitalizations eg for AL induction or for
HSCT, the study group of patients were shifted from oral
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009
hypoglycemic agents to insulin therapy so as to have an
optimal control of their blood glucose levels.
CONTROL PATIENTS
The control group of patients consisted of all patients
with AL treated at both institutions during the study period
but never had pre-existing DM present at the time of AL
presentation. This group included 401 patients with various
types of AL (201 AML, 188 ALL and 12 ABL). There were
237 males and 164 females and their ages ranged between
14 and 75 years with a median age of 29 years.
Both groups of patients received the same
chemotherapeutic protocols to control their leukemias.
They were also given the same HSCT conditioning
protocols and the same immunosuppressive therapies.
RESULTS
A total of 408 patients with AL were treated at both
institutions during the study periods specified previously.
Only 7 patients had pre-existing DM at the time of the
diagnosis of AL. The incidence of DM in adult patients
with AL was 1.72%. Among the 5 patients with AML, 3
patients had M5 type, 1 M6 type and 1 M3 type of AML.
Three study patients had chromosomal abnormalities and
3 had extramedullary disease at presentation of their
leukemias. All the 7 study patients received cytotoxic
chemotherapy to control their hematological malignancies.
They were given a median of 3 courses of chemotherapy
per patient. Three study patients were refractory and 4
patients were responsive to cytotoxic chemotherapy,
although the degree of responsiveness / refractoriness to
chemotherapy was variable. Four study patients received
allogeneic HSCTs. Out of these HSCT recipients, 2 had
GVHD and 2 did not have it. The GVHD was mild in 1
patient and severe in the other one. All the patients with
DM and AL had infectious complications: 2 had Klebsiella
pneumoniae bacterermias and 2 had candidemias. Follow
up of these patients showed that 4 patients were alive and
3 patients were dead at the end of the study period. The
causes of death in the deceased patients were as follows:
1 due to progressive and refractory AL, 1 due to HSCT
complications namely recurrent infections and severe
GVHD and 1 due to severe infections and multiorgan
failure following the induction course of chemotherapy
given to control the AL. Out of the 4 alive patients; 3
patients had no relapses and 1 patient had a single relapse
which was controlled by a reinduction course of
chemotherapy followed by a second allogeneic HSCT
(Table 1).
pp 235-238 34
 Table 1: shows details of the primary hematological disorders in the study patients

Number Age Sex Diagnosis Cytogenetic EMD No of Response to HSCT HSCT Infections Out come:
findings CCC chemotherapy Done/ Compli- encountered Dead/Alive
Not done cations

1 67 M AML, M3 t15,17 Absent 6 Excellent Not done --- Klebsiella Alive, no

response sepsis relapses

2 46 M AML, M6 None Absent 3 Partially Done Severe Recurrent Death due to

refractory infections, infections &
negative GVHD
cultures

3 24 F AML, M5 t 9,11 Present 5 Partially Done Mild Klebsiella Alive,

[tonsils] refractory 2 allogeneic GVHD sepsis, 1 relapse
HSCT Candidemia, post-first
E. coli (UTI) HSCT

Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009

4 42 M AML, M5 None Absent 3 Excellent Done No Febrile Alive,
response GVHD neutropenias, no
(negative cultures) replapses

5 39 F AML, M5 None Present 3 Responsive Done No Febrile Alive,

[CNS] GVHD neutropenias, no
(negative cultures) relapses

6 45 F ABL t 9,22. Present 2 Refractory Not done -- Febrile Death due to

(skin) neutropenias progressive
disease

7 50 M Pre-B t 8, 29 Absent 1 Good Not done -- Candida Death due to

ALL response tropicalis, severe
gram-nagative infections&
sepsis multi-system
failures

AML: acute myeloid leukemia EMD: extramedullary leukemia HSCT: hematopoietic stem cell transplant
ALL: acute lymphoblastic leukemia CCC: courses of cytotoxic chemotherapy GVHD: graft versus host disease
ABL: acute biphenotypic leukemia CNS: central nervous system UTI: urinary tract infection
The Negative Correlation Between Diabetes Mellitus and Acute Leukemia in ........

35
Khalid Ahmed Al-Anazi

Regarding the details of DM in the patients studied; all of
them had type 2, adult onset, non-insulin dependent DM.
They were having DM for a median duration of 13 years
before the diagnosis of AL. All the diabetic patients with
AL had previously been treated with oral hypoglycemic
agents. Only 2 study patients had the 3 major complications
of DM: nephropathy, retinopathy and neuropathy
together. The control of DM was good in 5 patients and
poor in the other 2 patients. The poor control of DM in
patients with AL was mainly due to non-compliance with
drug therapy. The median body mass index (BMI) was
31.6 (obese): one patient had a normal BMI, two patients
were overweight and four patients were obese (Table 2).
The median age of the study group was higher than that
of the control group of patients (45 versus 29 years). AML
was the predominant type of AL encountered in the study
group (71.4%), while it was only slightly commoner than
ALL in the control group. Infections affected all the study
patients , while 54.6% of the control group of patients
developed infectious complications. The AL was more
refractory to treatment in the study group of patients
(42.9% vs 5%). Extramedullary disease was seen in 42.9%
of the study patients and in 11% of the control patients.
The death rate was also higher in the study group of
patients (42.9% vs 33.3%). Interstingly, both groups of
patients had similar rates (approximately 57%) of
chromosomal abnormalities. Also, the relapse rate of AL
was lower in the study group compared to the control group
of patients (14.3% vs 40%). The mortality in the study
group was due to infectious complications in two thirds of
the deceased patients, while pregressive uncontrolled
leukemia caused death in the remaining one third of
patients. On the other hand, infections caused death in
one third of the control patients, while relapsing/refractory
AL caused death in two thirds of the deceased patients
(Tables 1 and 3).

Table 2: shows details of DM in the study patients

Number BMI Type of Duration of Treatment Complications Control of

DM DM before given forDM of DM DM during
the diagnosis hospitalizations
of leukemia & follow up

1 24 2 18 years oral agents retinopathy, good

(normal) nephropathy and
neuropathy

2 27.5 2 14 years oral agents retinopathy poor

(overweight)

3 34.1 2 6 years oral agents none good

(obese)

4 38 2 13 years oral agents retinopathy good

(obese) then insulin

5 31.6 2 10 years oral agents none good

(obese)

6 26.5 2 11 years oral agents retinopathy good

(overweight)

7 36 2 16 years oral agents retinopathy, poor

(obese) nephropathy and
neuropathy

DM: diabetes mellitus BMI: body mass index

Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009 pp 235-238 36
 Table 3: shows details of the control group of patients

Type of Number Alive Deceased HSCT Relapses Refractory Chromosomal Infections encountered
acute of patients patients disease abnormalities
leukemia patients

CMV Bacterial Fungal

No % No % No % No % No % No % No % No % No % No %

AML 201 50.1 147 73 54 26.9 94 46.8 57 28.4 10 5.0 115 57.2 36 17.9 70 34.8 9 4.5

Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009

ALL 188 46.9 115 61.2 73 38.8 60 31.9 97 51.6 6 3.2 107 56.9 21 11.2 68 36.2 7 3.7

ABL 12 3.0 5 41.7 7 58.3 5 41.7 6 50.0 4 33.3 6 50.0 2 16.7 4 33.3 2 16.7

Overall 401 100.0 267 66.6 134 33.3 159 39.7 160 40.0 20 5.0 228 56.9 59 14.7 142 35.4 18 4.9
numbers and
percentages

HSCT : Hematopoietic stem cell transplant No : Number

AML : Acute myeloid leukemia % : Percentage
ALL : Acute lymphoblastic leukemia CMV : Cytomegalovirus
ABL : Acute biphenotypic leukemia
The Negative Correlation Between Diabetes Mellitus and Acute Leukemia in ........

37
Khalid Ahmed Al-Anazi
DISCUSSION
The incidence of childhood-onset, type 1, DM varies
markedly between countries.10 An increasing incidence
rate of this type of DM has been described in several
countries, particularly amongst the youngest children and
the Nordic countries have consistently been shown to have
the highest incidence rates.11 Enterovirus infections had
previously been linked to the development of type 1 DM,
but more recent studies performed in seven European
countries have shown an inverse correlation between the
incidence of diabetes and enterovirus infections in the
background population.11 Although some studies have
shown a significant positive correlation between the
incidence rates of ALL and type 1 DM as both share
common epidemiological and environmental features, other
studies have shown negative correlation and temporal
trends in the incidences of both disorders when these
incidences were analyzed in well-defined populations.12,13
The age adjusted prevalence of DM in both sexes in Saudi
Arabia ranges between 4.3% and 12.3%.14-17 Some studies
have shown a higher prevalence of DM in males, while
others have shown a higher prevalence of DM in
females.14,16-20 The prevalence of DM increases with: age,
obesity and the socio-economic class.14,15,18-20 According
to a large study performed in Riyadh, the prevalence of
DM in individuals above the age of 15 years in urban
population was 12% for males and 14% for females and
that in rural population was 7% for males and 7.7% for
females. 19 The age adjusted prevalence of DM was
significantly higher in urban than in rural populations and
was amongst the highest in the world.19 The prevalence of
DM was highest (49%) in females aged 51-60 years and
lowest (2%) in patients aged 15-20 years in urban
populations whilst in rural populations, the prevalence of
DM was highest (29%) in females above 60 years of age
and lowest (1%) in patients between 15 and 20 years of
age. The study also showed an association between DM
and old age, obesity as well as family history of DM.19
The importance of adipose tissue in metabolism, as a target
for insulin action and as a secretor of metabolic regulatory
proteins is increasingly recognized. 21 Lipodystrophic
conditions are often associated with a significant degree of
insulin resistance. The late sclerodermatous form of GVHD
following allogeneic HSCT is an acquired lipodystrophic
condition.21 In patients who develop DM following the
sclerodematous chronic GVHD occurring after allogeneic
HSCT, the best glycemic control can be achieved with a
combination of metformin and highly concentrated soluble
insulin injections.21 Post-transplant DM has been reported
to occur in 5-15% of non-diabetic renal transplant recipients
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009
(in 29.6% of Arab transplant recipients and only in 1.7%
non-Arabs).22
Two haplotypes in the 2 adjacent blocks in AMACO gene,
a von Willeband factor homologue, appear to be associated
with the absence of type 1 DM.23 Interestingly, in both
haplotype blocks, a single nucleotide polymorphism (SNP)
distinguishes the protective haplotype from the other
haplotype. One SNP is non-coding, whereas the other SNP
causes a change from glutamic acid to glycine. 23
Hyperglycemia may induce hyperosmotic responses
including apoptosis in vascular endothelium and
leucocytes. Hyperosmolar shock can elicit a stress response
in mammalian cells, often leading to apoptotic cell death.24
Resveratrol, a phytoalexin present in grapes, has antioxidant
as well as anti-inflammatory properties. The apoptotic
biochemical changes are blocked by the antioxidant
pretreatment with resveratrol during the hyperosmotic
shock-induced cell death. Resveratrol has been shown to
attenuate the high glucose induced apoptotic changes
including: C-Jun N-terminal Kinase (JNK) activation and
caspase-3- activation in human leukemia K562 cells.24 High
glucose-treated K562 cells have displayed a lower degree
of attachment to collagen, the major component of the
vessel wall subendothelium. In contrast, cells pre-treated
with resveratrol followed by high glucose have been shown
to exhibit a higher affinity for collagen.24
In UK and USA, the diabetes risk was found to be higher
in twins who were heterozygous for DR3-DQ2 and DR4-
DQ8 than in twins with neither DR3-DQ2 nor DR4-DQ8.25
Monozygotic twins of patients with type 1 DM had similar
rates of progression to diabetes. Whereas most twins did
not develop DM, 25% of the twins who progressed did so
after 14 years of discordance. An age-related heterogeneity
was observed, with higher progression to DM for twins of
patients diagnosed at a younger age.25 DM and AL [both
ALL and AML] have been reported to coexist in patients
with certain chromosomal abnormalities eg Werner
syndrome, Sotos syndrome, Alstrom syndrome and Bloom
syndrome.26-29
Recently, the field of complex disease genetics has
witnessed rapid progress, particularly following the advent
of genome-wide association scans (GWAS).30 The genome-
wide association studies have revealed an increase in the
number of confirmed type 2 diabetes susceptibility loci from
three (PPARG, KCNJ11 and TCF7L2) to nine (with the
addition of: CDKAL1, CDKN2A/B, IGF2BP2, HHEX/
IDE, FTO and SLC30A8).9,30 These studies have improved
our understanding of the genetic etiology of type 2 DM
and provided invaluable insights into the way genetic
studies should be conducted. However, replication of the
pp 235-238 38
 The Negative Correlation Between Diabetes Mellitus and Acute Leukemia in ........
major GWAS findings in diverse populations, fine mapping
of the association signals and extensive sequencing of
implicated genes should form the next step in the field of
type 2 DM genetics.30
The therapeutic approach to AML is based on
chemotherapy, but the side effects of the drugs used and
the other complications namely infections and bleeding
are sometimes fatal.31 In patients with ALL, with the
improvements in chemotherapy and in supportive care, the
rate of complete remission (CR) ranges between 75% and
90%, while long-term disease-free survival remains
unsatisfactory (30-40%).32 Allogeneic HSCT has been
successfully used for many years to treat a variety of
hematological malignancies. Depending on the underlying
disease condition, allogeneic HSCT results in long-term
complete response in up to 80% of patients with best results
achieved when transplantation is performed during the
first CR of AL.33,34 Infections with a diverse group of
organisms remain the leading causes of morbidity and
mortality in patients with malignant disorders and in
recipients of HSCT despite the use of infection prophylaxis,
growth factors and the new antimicrobial agents and despite
the recent advances in the supportive care over the past
decade.35,36 The main risk factors for infections in patients
with malignant disorders are: uncontrolled malignancy,
immunosuppressive and cytotoxic chemotherapy and
immunological defects including T-cell depletion and
hypogammaglobulinemia.37 The risk of infection is directly
proportional to the intensity and duration of cytotoxic
chemotherapy and immunosuppressive treatment. 37
Despite having a lower relapse rate, our study group of
patients had a higher degree of resistance to chemotherapy
and thus the number of study patients subjected to
allogeneic HSCT were higher than that in the control group.
Infections were encountered in all the study patients and
they were the causes of death in two thirds of the deceased
patients. On the other hand, infections were encountered
in only slightly more than half of the control patients and
they were the causes of death only in one third of the
deceased patients. The explanation for the latter finding is
that DM further suppresses the immunity of patients with
AL and thus makes them more susceptible to infectious
complications.
According to the Saudi tumor registry, leukemia has been
ranking the second commonest malignancy at all ages and
in both sexes since the year 1975 and it has been the most
common malignancy in children, with ALL being the
commonest childhood cancer.38 Local studies have also
shown that diabetes is a very common chronic health
disorder and that the prevalence of this disease is amongst
the highest in the world.14-20 Consequently, the likelihood
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009
of having both disorders coexisting in the same patient is
expected to be high. Surprisingly, our study showed that
the incidence of DM in adult patients with AL was
extremely low in comparison to the the prevalence of DM
in the adult Saudi population. Interestingly, there are no
reports or major studies on the prevalence of DM in adult
patients with AL not only in the developing countries but
also in Europe and North America.
Despite including a relatively large number of patients
with AL from two major tertiary care centers in Saudi
Arabia, we aknowledge that the number of patients having
both DM and AL is rather small and we also aknowledge
the limitations of retrospective studies. Observing the
recent advances in the era of genomics, we hope that this
study will encourage hematologists, endocrinologists,
cytogenetists and other researchers to perform larger
prospective multicentric studies to determine the real
prevalence of DM in patients with AL and to explore any
possible underlying genetic or other pathological basis for
our observations.
CONCLUSION
DM and leukemia are common health problem not only
in Saudi Arabia but also in many other populations. Our
study showed the following interesting and first reported
findings: (1) a clear negative correlation between DM and
AL in the adult Saudi population. (2) adult patients with
DM tended to develop AL at an older age and were more
likely to have AML form of leukemia. (3) higher rates of
infection, mortality, extramedullary disease and
refractoriness to chemotherapy but a lower relapse rate in
the diabetic than the non-diabetic patients having AL.
The possibility that adult patients with DM may have
certain genes that have protective effects against the
development of AL may explain the lower incidence of
AL in adult patients with DM.
ACKNOWLEDGEMENTS
We are grateful to all medical, nursing and technical staff
who participated in the management of the patients presented
at the Armed Forces Hospital and King Faisal Specialist Hospital
and Research Centre in Riyadh, Saudi Arabia.
REFERENCES
1 Osei K. Global epidemic of type 2 diabetes: implications for
developing countries. Ethn Dis 2003, 13: S102-106 (ISSN:
1049-510X).
2 Dagago- Jack S. Primary prevention of type-2 diabetes in
developing countries. J Natl Med Assoc 2006, 98: 415 – 419.
3 Bjork S, Kapur A, King H, Nair J, Ramachandran A. Global
39
Khalid Ahmed Al-Anazi
policy: aspects of diabetes in India. Health Policy 2003, 66:
61-72.
4 Tripathi BK, Srivastava AK. Diabetes mellitus: complications
and therapeutics. Med Sci Monit 2006, 12: RA 130-147.
5 Sartorelli DS, Franco LJ. Trends in diabetes mellitus in Brazil:
the role of the nutritional transit. Cad Saude Publica 2003, 19:
S29-36 (ISSN: 0102-311X).
6 Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence
of diabetes: estimates for the year 2000 and projections for 2030.
Diabetes Care 2004, 27: 1047-1053.
7 Motala AA, Omar MA, Pirie FJ. Diabetes in Africa.
Epidemiology of type 1 and type 2 diabetes in Africa. J Cardiovasc
Risk 2003, 10: 77-83.
8 Tomisaka K, Lako J, Maruyama C et al. Dietary patterns and
risk factors for type 2 diabetes mellitus in Fijian, Japanese and
Vietnamese populations. Asia Pac J Clin Nutr 2002, 11: 8-12.
9 Kozieradzka A, Kaminski K, Pepinski W et al. The association
between type 2 diabetes mellitus and A1/A2 polymorphism of
glycoprotein III a gene. Acta Diabetol 2007, 44: 30-33.
10 Viskari H, Ludvigsson J, Uibo R et al. Relationship between the
incidence of type 1 diabetes and enterovirus infections in
different Europian populations; results from the EPIVIR project.
J Med Virol 2004, 72: 610-617.
11 Joner G, Stene LC, Sovik O. Nationwide, prospective registration
of type 1 diabetes in children aged < 15 years in Norway 1989-
1998: no increase, but significant regional variation in incidence.
Diabetes Care 2004, 27: 1618-1622.
12 Feltbower RG, Mckinney PA, Greaves MF, Parslow RC,
Bodansky HJ. International parallels in leukemia and diabetes
epidemiology. Arch Dis Child 2004, 89: 54-56.
13 Richiardi L, Magnani C, Bruno G, Maule MM, Merletti F,
Pastore G. Re-detecting small area similarities in the
epidemiology of childhood acute lymphoblastic leukemia and
diabetes mellitus; type 1: a bayesian approach. Am J Epidemiol
2005, 162: 1132-1133.
14 Fatani HH, Mira SA, El-Zubier AG. Prevalence of diabetes
mellitus in rural Saudi Arabia. Diabetes Care 1987, 10:
180-183.
15 Anokute CC. Epidemiologic studies of diabetes mellitus in
Saudi Arabia—Part 1—Screening of 3158 males in King Saud
University. J R Soc Health 1990, 110: 201-203.
16 Abu-Zeid HA, Al-Kassab AS. Prevalence and health care
features of hyperglycemia in semiurban-rural communities in
southern Saudi Arabia. Diabetes Care 1992, 15: 484-489.
17 Kulaylat NA, Narchi H. A twelve year study of the incidence of
childhood type 1 diabetes mellitus in the Eastern Province of
Saudi Arabia. J Pediatr Endocrinol Metab 2000, 13: 135-140.
18 Warsy AS, El-Hazmi MA. Diabetes mellitus, hypertension and
obesity-common multifactorial disorders in Saudis. East
Mediterr Health J 1999, 5: 1236-1242.
19 Al-Nuaim AR. Prevalence of glucose intolerance in urban and
rural communities in Saudi Arabia. Diabet Med 1997, 14:
595-602.
20 Karim A, Ogbeide DO, Siddiqui S, Al-Kharila IM. Prevalence
of diabetes mellitus in a Saudi community. Saud Med J 2000,
Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No.1, January 2009
21: 438-442.
21 Rooney DP, Ryan MF. Diabetes with partial lipodystrophy
following sclerodermatous chronic graft vs host disease. Diabet
Med 2006, 23: 436-440.
22 Shaltout AA, Moussa MA, Qabazard A et al. Further evidence
for the rising incidence of childhood type 1 diabetes in Kuwait.
Diabet Med 2002, 19: 522-525.
23 Eller E, Vardi P, Daly MJ et al. IDDM 17: polymorphisms in the
AMACO gene are associated with dominant protection against
type 1A diabetes in a Bedouin Arab family. Ann N Y Acad Sci
2004, 1037: 145-149.
24 Chan WH. Effect of resveratrol on high glucose-induced stress
in human leukemia K 562 cells. J Cell Biochem 2005; 94:
1267-1279.
25 Redondo MJ, Yu L, Hawa M et al. Heterogeneity of type 1
diabetes; analysis of monozygotic twins in Great Britain and
the United States. Diabetologia 2001, 44: 354-362.
26 Ochi M, Igase M, Nagal A et al. A case of Werner syndrome
with chromosomal abnormality. Nippon Ronen Igakki Zasshi
2006, 43: 639-642.
27 Al-Mulla N, Belgaumi AF, Tecbi A. Cancer in Sotos syndrome:
report of a patient with acute myelocytic leukemia and review
of the literature. J Pediatr Hematol Oncol 2004, 26: 204-208.
28 Chen BH, Chiou SS, Tsai RK, Lin YF, Wu JR. Acute
lymphoblastic leukemia in one of two siblings with Alstorm
syndrome. J Formos Med Assoc 2000, 99: 792-795.
29 Bhisitkul RB, Rizen M. Bloom syndrome: multiple retinopathies
in a chromosome breakage disorder. Br J Ophthalmol 2004, 88:
354-357.
30 Ziggini E. A new era for Type 2 diabetes genetics. Diabet Med
2007, 24: 1181-1186.
31 Kizak M. New therapeutic approach for myeloid leukemia:
induction of apoptosis via modulation of reactive oxygen species
production by natural compound. Int J Hematol 2006, 83 :
283-288.
32 Vitale A, Guarini A, Chiaretti S, Foa R. The changing scene
of adult acute lymphoblastic leukemia. Curr Opin Oncol 2006,
18: 652-659.
33 Armitage JO. Bone marrow transplantation. N Engl J Med
1994, 330: 827.
34 Thomas ED. Karnofsky Memorial Lecture. Marrow
transplantation for malignant diseases. J Clin Oncol 1983,
1: 517.
35 Neuburger S, Maschmeyer G. Update on management of
infections in cancer patients and stem cell transplant patients.
Ann Hematol 2006, 85: 345-356.
36 George B, Mathews V, Srivastara A, Chandy M. Infections
among allogeneic bone marrow transplant recipients in India.
Bone Marrow Transplant 2004, 33: 311-315.
37 Smiley S, Almyroudis N, Segal B. Epidemiology and
management of opportunistic infections in immunocompromised
patients with cancer. Abstr Hematol Oncol 2005, 8: 20–30.
38. The Saudi national tumor registry annual report (2003), Tables:
2,5,9,10 and Figures: 5-7, 10-12, Pages: 12-30.
40