Nonmyeloablative Donor Stem Cell Transplant in Treating Patients with Congenital Anemias including Sickle Cell Disease and Thalassemia

Inclusion Criteria

• Sickle cell disease - patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end-organ damage (A, B, C, D, or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F): * A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral magnetic resonance imaging (MRI) or an abnormal trans-cranial Doppler examination (>= 200 m/s); or * B. Sickle cell related renal insufficiency defined by a creatinine level >= 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy or nephrotic syndrome or creatinine clearance < 50 mL/min or requiring peritoneal or hemodialysis; or * C. Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of >= 2.5 m/s at least 3 weeks after a vaso-occlusive crisis; or * D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting >= 4 hours involving the corpora cavernosa and corpus spongiosa; or * E. Sickle hepatopathy defined as either ferritin > 1000 mcg/L or direct bilirubin > 0.4 mg/dL at baseline; or
• F. Any one of the below complications * Vaso-occlusive crises; eligible for hydroxyurea*: at least 3 hospital admissions in the last year; eligible for hematopoietic stem cell transplantation (HSCT): more than 1 hospital admission per year while on maximal tolerated dose of hydroxyurea* * Acute chest syndrome (ACS); eligible for hydroxyurea*: 2 prior ACS while > 3 years of age and adequately treated for asthma; eligible for HSCT: any ACS while on hydroxyurea* * Osteonecrosis of 2 or more joints; eligible for hydroxyurea*: and significantly affecting their quality of life by Karnofsky score 50-60; eligible for HSCT: and on hydroxyurea* where total hemoglobin increase less than 1 g/dL or fetal hemoglobin increases < 2.5 times the baseline level * Red cell alloimmunization; eligible for hydroxyurea*: transfusion-dependent; eligible for HSCT: total hemoglobin increase < 1 g/dL while on hydroxyurea* * Note: hydroxyurea at maximum tolerated dose
• Thalassemia - patients with thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following: * Portal fibrosis by liver biopsy * Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with desferroxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week) * Hepatomegaly of greater than 2 cm below the costochondral margin
• 6/6 human leukocyte antigen (HLA) matched family donor available
• Ability to comprehend and willing to sign an informed consent, assent obtained from minors
• Negative serum beta-human chorionic gonadotropin (HCG)
• DONOR: 6/6 HLA identical family donor
• DONOR: Weight > 20 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses)
• DONOR: Fit to receive G-CSF (filgrastim) and give peripheral blood stem cells (normal blood counts, normotensive, and no history of stroke)
• DONOR: Ability to comprehend and willing to sign an informed consent

Exclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more or Lanksy performance status of < 40
• Diffusion capacity of carbon monoxide (DLCO) < 50% predicted (corrected for hemoglobin and alveolar volume)
• Baseline oxygen saturation of < 85% or partial pressure of oxygen in arterial blood (PaO2) < 70
• Left ventricular ejection fraction: < 40% estimated by echocardiogram (ECHO)
• Transaminases > 5x upper limit of normal for age
• Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen
• Major anticipated illness or organ failure incompatible with survival from peripheral blood stem cell (PBSC) transplant
• Pregnant or lactating * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Major ABO mismatch
• DONOR: Pregnant or lactating * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• DONOR: Human immunodeficiency virus (HIV) positive
• DONOR: Hemoglobin S >= 50%, or beta thalassemia intermediate