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The Role of Genetic Polymorphisms in Innate Immune Response Genes in Susceptibility to Infections

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Trial Information

The Role of Genetic Polymorphisms in Innate Immune Response Genes in Susceptibility to Infections

A small number of patients will develop severe infection after chemotherapy or after
allogeneic bone marrow transplantation. The ability of patients with leukemia or bone marrow
transplantation to fight infections is decreased. One reason is that chemotherapy
transiently destroys the type of white blood cells called neutrophils. Neutrophils are the
first line of defense of our body against infections. Bone marrow transplant patients may be
receiving edications to prevent graft versus host disease. Such medications may decrease the
ability of the body to fight infections.

People respond to infections in different ways. Some may be born with genes that make them
more likely to get certain types of infections. Specific genes may affect the response to
different microbes (pathogens). We want to find out which genes have normal changes in them
and lead to different responses to infections. We also want to find out how the ability to
fight infections is related to the way these genes work.

Responses to infection are controlled by our immune system. Changes in genes of the immune
system that may alter control of infection may make people more susceptible to some types of
lymphoma The goals of this study are:

1. Find out if some people are more likely to get severe infections, than others. To do
this we will compare patients with leukemia who develop severe infections to patients
who do not develop infections.

2. Find out if some people are more likely to develop lymphoma than others. To do this we
will compare patients with lymphoma to people without lymphoma who are of the same sex
and similar age and ethnic background to the patients with lymphoma.

The purpose of this study is to better understand genetic susceptibility to infections and
the interactions of specific genetic polymorphisms of innate immune receptors with microbial
and fungal organisms.

To accomplish this, blood specimens from patients with acute myeloid leukemia, RAEB, RAEBT
or acute lymphocytic leukemia, follicular or mantle cell lymphoma or recipients of
allogeneic hematopoietic stem cell transplants (HSCT) will be collected. We will genotype
the genes of innate immune receptors to identify genetic polymorphisms associated with
higher frequency of invasive infections or susceptibility to lymphoma. All specimens will be
processed in the Infectious Diseases Laboratory at MSKCC. RNA will be extracted from
peripheral blood mononuclear cells (PBMCs). Genotyping will be done from genomic DNA or from
cDNA generated from RNA by RT-PCR. Cell lines will be created from PBMCs and will be
analyzed in functional assays for responses to bacterial and fungal products (cytokine
secretion, upregulation of cell surface molecules). All patient samples including genomic
DNA, RNA, cDNA and cell lines will be banked in the Infectious Disease laboratory at MSKCC.

In order to perform this study, patients diagnosed with acute leukemia will be asked to
provide blood, and permission to review the medical charts. We will collect (removed
prospectively) data regarding risk factors for infections, diagnosis of infections, response
to treatment and outcome.

Inclusion Criteria:

- Subject must either:

1. Have histologically confirmed acute myeloid leukemia (AML), acute lymphocytic
leukemia (ALL), follicular or mantle cell lymphoma RA-EB, RAEB-T newly diagnosed
at first or second remission AND are going to receive or have received
myelosuppressive chemotherapy; OR

2. Will receive or have received allogeneic HSCT for hematologic malignancy.

- Subject has signed informed consent before entering the study.

Participation of children: For subjects under the age of 18, we will obtain the subject's
and their parents' approval to enroll them.

Exclusion Criteria:

- Subject has been diagnosed with leukemia other than acute myeloid leukemia RA-EB or
RAEB-T or acute lymphocytic.

- Subject is not going to receive chemotherapy or has not received chemotherapy.

- Subject will undergo/had undergone HSCT for disease other than hematologic

Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Prospective

Outcome Measure:

Risk for developing infection or lymphoma due to allelic variation in genes of immune system that specialize in pathogen recognition compared to absence of allelic variation.

Outcome Time Frame:

6 years

Safety Issue:


Principal Investigator

Genovefa Papanicolaou, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

February 2003

Completion Date:

January 2011

Related Keywords:

  • Infections
  • Infections
  • lymphoma
  • Disease Susceptibility



Memorial Sloan Kettering Cancer Center New York, New York  10021