iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy

Participants will be recruited from an existing protocol at St. Jude (SJLIFE, NCT00760656).
Complete neuropathic evaluations are obtained as part of SJLIFE, and the information will be
shared for use in the SJLPSC study. A one-time blood draw will be obtained, and peripheral
blood mononuclear cells (PBMC's) will be isolated for eventual creation of induced
pluripotent stem cells (iPSC) that will be differentiated into human neurons. These human
neurons will allow the investigators to functionally validate and further interrogate CEP72
genetic variants or variants in other genes that are associated with persistent (or acute)
vincristine neuropathy using a "state of the art" cellular model of human neurons.
Furthermore, creating neurons from patients at the extremes (highly sensitive to
vincristine-induced neuropathy and matched controls) allows the study of differences at
baseline and after treatment with vincristine.

PRIMARY OBJECTIVE:

- To establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who
did or did not develop persistent treatment-induced peripheral neuropathy, from which to
make human neurons to assess their sensitivity to vincristine and determine whether
neurons from patients who developed neuropathy are more sensitive to vincristine or
other neurotoxic chemotherapy.

SECONDARY OBJECTIVE:

- To evaluate the iPSC neurons made from patients with persistent treatment-related
neuropathy and iPSC neurons from patients who did not develop neuropathy from the same
treatment, for phenotypic difference prior to and after exposure to vincristine or other
potentially neurotoxic medications.

Inclusion Criteria - Neuropathy Patients:

- Adult survivor of childhood ALL

- Presence of any neuromotor, neurocortical, or neurocerebellar toxicity after
vincristine treatment (either acute and/or persistent neuropathy)

- At least 50% of the persistent vincristine neuropathy cases will have the CEP72
promoter variant (rs924607) or a coding variant in CEP72 that is predicted to be
damaging (CADD score >9). The balance of neuropathy cases will either have variants in
other genes that are associated with vincristine neuropathy identified in the ongoing
genome-wide association study (GWAS) of 1250 St. Jude Life ALL survivors, or have
neuropathy in the absence of known genetic variants altering the risk of neuropathy.

- Patient understands the nature of the study and provides informed consent

Inclusion Criteria - Controls:

- Adult survivor of childhood diagnosis of ALL

- Absence of persistent neurotoxicity (grade 0) after completion of a standard
vincristine-containing chemotherapy regimen (may or may not have experience acute
neuropathy during treatment.

- Matched to a specified subject with neurotoxicity based on age (within 5 years), tumor
type, chemotherapy regimen or total vincristine dosage, race and ethnicity.

- At least 50% of the controls will have the CEP72 promoter variant T/T genotype (at
rs924607) or a coding variant in CEP72 that is predicted to be damaging (CADD score
>9). The balance of controls will either have variants in other genes that are
associated with vincristine neuropathy identified in the ongoing GWAS of 1250 St. Jude
Life ALL survivors, or will not have a known genetic variant altering the risk of
neuropathy.

- Patient understands the nature of the study and provides informed consent

Inclusion of Women and Minorities:

- Individuals of both genders, all races and ethnic groups are eligible for this
protocol.

Exclusion Criteria - Both Cohorts:

- Treatment with other severely neurotoxic chemotherapy (i.e. cisplatin) prior to or
concomitantly with vincristine. Carboplatin therapy is allowed

- Presence of peripheral neuropathy prior to vincristine therapy

- Poorly controlled or insulin-dependent diabetes or other condition likely to
predispose to neurotoxicity