Crohn's Allogeneic Transplant Study

Inclusion Criteria: * A diagnosis of CD established by referring physician(s) and confirmed by our review of the clinical presentation, clinical course, endoscopic and imaging findings, and histology of mucosal tissue specimens * An adverse prognosis, documented by persistent signs and symptoms of CD that have failed to respond satisfactorily to medical and surgical therapies in the past, including but not limited to systemic immune suppressive drugs and biopharmaceuticals; to be considered as refractory to medical and surgical therapy, there must be clinical, endoscopic, and histologic evidence of active inflammatory Crohn's Disease that has either persisted or recurred despite exhaustive treatment with available pharmaceutical and surgical therapies; exhaustive treatment is defined as prior exposure to the following, without durable improvement: * Systemic glucocorticoids at or above a prednisone equivalent of 40 mg/day for at least 2 weeks, or until drug toxicity or intolerance develops * Methotrexate (25 mg per week for at least 3 months, or until drug toxicity or intolerance develops) and/or a thiopurine antimetabolite (either 2.5 mg/kg azathioprine or 1.5 mg/kg 6-mercaptopurine in patients homozygous wild-type for the thiopurine-S-methyltransferase \[TPMT\] gene, or either 1.5 mg/kg azathioprine or 1 mg/kg 6-mercaptopurine in patients heterozygous for TPMT, or doses of these drugs capable of producing a 6-thioguanine nucleotide level of 230-400 without producing a 6-methylmercaptopurine nucleotide level above 5700 for at least 3 months, or until drug allergy, intolerance or toxicity develops); if a patient is homozygous mutant for the TPMT gene, thiopurines would be contraindicated and their use would not be a requirement for enrollment in this protocol * Use of at least two anti-tumor necrosis factor (TNF)-alpha therapies, that is, infliximab (at least 5 mg/kg every 8 weeks for at least 3 months, or until drug allergy, toxicity or intolerance or anti-infliximab antibodies develop) and/or adalimumab (at least 40 mg subcutaneously \[SQ\] every 2 weeks for at least 3 months, or until drug allergy, toxicity or intolerance develops) and/or certolizumab pegol (at least 400 mg SQ every 4 weeks for at least 3 months, or until drug allergy, toxicity or intolerance develops) * Due to the serious risk of progressive multifocal leukoencephalopathy (PML) and the reluctance of some patients to agree to therapy that carries such risk, prior exposure to natalizumab is not required to meet the definition of exhaustive pharmaceutical treatment; neither will use of natalizumab among patients who are John Cunningham (JC) virus antibody seronegative be an exclusionary criterion * Exhaustive surgical treatment will be defined as indicated operations for complications of Crohn's Disease up to the point where the risks of surgery (for example, mortality or post-operative morbidity such as short bowel syndrome or extensive adhesions with high risk for inadvertent enterotomy) are deemed by patients and their physicians to be unacceptably high; indicated operations for complications of Crohn's Disease include, but are not limited to, surgical resection of involved intestine, stricturoplasty, drainage, curettage, or adhesiolysis of tissues affected by Crohn's disease * Exposure of patients to investigational drug therapies for Crohn's Disease, that is, to drugs that are not Food and Drug Administration (FDA) approved for this indication, will not be a criterion for either inclusion or exclusion * Endoscopic and histologic evidence of active intestinal inflammation consistent with CD; in the event that the involved mucosa cannot be readily reached by endoscopic biopsy, an imaging test that shows typical changes of CD in the intestinal tract will suffice as evidence of active intestinal inflammation; the presence of intestinal stomas does not exclude the patient from study * Severe CD as defined by one of the following: * CDAI \>= 250 * Need for total parenteral nutrition to maintain weight * Recurrent intestinal inflammation caused by CD following surgical resection * Identification of a HLA-matched hematopoietic cell donor without a history of a disorder that can be transmitted by hematopoietic cells, including but not limited to inflammatory bowel disease, and without nucleotide-binding oligomerization domain containing 2 (NOD2) mutations in the case of a HLA matched sibling * DONORS will be a HLA-identical sibling or HLA-matched unrelated donor; unrelated donors are required to be matched by high resolution allele level typing for HLA-A, B, C and DRB1 and intermediate resolution Sequence Specific Oligonucleotide Probes (SSOP), identifying alleles in groups of related families historically defined as antigens for DQB1; an unrelated donor is considered matched if patient and donor share HLA-A, B, C alleles with identical sequences at exons 2 and 3, DRB1 alleles with identical sequences at exon 2, and DQB1 results that include the same allele groups * DONORS will have the ability to understand and the willingness to sign a written informed consent document for bone marrow harvest. Exclusion Criteria: * A current complication of CD that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: * Abscess, phlegmon, necrotizing skin lesion, or inflammatory fistula * Intestinal fibrotic stricture and intestinal obstruction * Uncontrolled mucosal, organ, or systemic infection with a bacterial, viral, fungal, or parasitic organism * Sclerosing cholangitis * History of progressive multifocal leukoencephalopathy * Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: * Renal insufficiency as defined by an estimated glomerular filtration rate (GFR) \< 60 mL/minute * Cardiac dysfunction as defined by symptomatic coronary artery disease, congestive heart failure, valvular heart disease, cardiomyopathy, uncontrolled arrhythmia(s), or left ventricular ejection fraction \< 50% * Pulmonary dysfunction that poses a risk of mortality after transplant, defined as pulmonary disease-moderate, using pre-transplant pulmonary function testing per the Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Manual * Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension * Marrow dysfunction that poses a risk of peri-transplant mortality, defined as an absolute neutrophil count or lymphocyte count below the lower limit of normal, or a platelet count below 50,000/mm\^3 * Poorly controlled hypertension despite appropriate therapy, defined as a diastolic blood pressure greater than 90 mm Hg while on therapy * Neurologic dysfunction that affects activities of daily living and medical care * Poorly controlled diabetes mellitus, defined as persistent hyperglycemia despite therapy or recurrent hypoglycemia while on therapy * Extreme protein-calorie malnutrition defined by body mass index \< 18 kg/m\^2 and unintentional weight loss (3 kg in the last month or 6 kg in the last 6 months) * Pregnancy * Fertile men or women unwilling to use contraceptive techniques during and for 12 months following transplant * History of smoking either tobacco or other herbal products in the last 3 months * Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) seropositivity * Patients whose life expectancy is severely limited by illness other than CD * Untreated psychiatric illness, including drug/alcohol abuse, that would compromise compliance * Inability to give voluntary informed consent or obtain a parent or guardian's informed consent * Demonstrated lack of compliance with prior medical care * History of a malignancy, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ * Hematopoietic cell transplant-co-morbidity Index greater than 2 * DONOR: Identical twin * DONOR: Pregnant or lactating females * DONOR: HIV seropositivity or presence of HBV deoxyribonucleic acid (DNA) or HCV ribonucleic acid (RNA) in the serum * DONOR: Current serious systemic illness including uncontrolled infections * DONOR: Malignancy within 10 years prior to donation of marrow, excluding adequately treated squamous cell skin cancer and basal cell carcinoma; treatment must have been completed (with the exception of hormonal therapy for breast cancer) with cure/remission status verified for at least 10 years at time of marrow harvest * DONOR: History of or symptoms consistent with inflammatory bowel disease or a serious autoimmune disorder * DONOR: Homozygous NOD2 mutation * DONOR: History of a serious disease or disorder that could be adoptively transferred by infusion of donor hematopoietic cells * DONOR: Failure to meet institutional criteria for donation as described in the Standard Practice Guidelines