Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
-22 Alemtuzumab 3mg IV (test dose)
-21 Alemtuzumab 10mg IV
-20 Alemtuzumab 15mg IV
-19 Alemtuzumab 20mg IV
-8 Fludarabine 30mg/m2 IV
-7 Fludarabine 30mg/m2 IV
-6 Fludarabine 30mg/m2 IV
-5 Fludarabine 30mg/m2 IV
-4 Fludarabine 30mg/m2 IV
-3 Melphalan 140mg/m2 IV
-2 Rest Day
-1 Rest Day
0 Stem Cell Infusion

Sickle Cell Disease

Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]
b) Medications
i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below

Alemtuzumab

I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine

Fludarabine

I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy.
II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.

Melphalan

Stem Cells

Hackensack University Medical Center

Stem Cell Transplantation for Sickle Cell Anemia

Reduced Intensity Stem Cell Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old

Primary endpoint:
In each group, the DFS at the 1 year endpoint will be estimated using the Kaplan Meier product limit estimator. The frequencies of the events, ie graft failure, will be enumerated and presented.

Secondary endpoints:
Overall survival: The distribution of time to death from any cause will be estimated by Kaplan- Meier product limit function and plotted. The overall survival will be measured from the time of transplant to any death and patients will be followed for 2 years.

Hackensack Meridian Health

After study enrollment, all subjects started anakinra (Kineret™; Amgen, Thousand Oaks, CA, USA) as a subcutaneous daily injection. Subjects weighing >25 kg at the time of enrollment received 100 mg daily, whereas those weighing <25 kg received 50 mg daily. Anakinra was continued for 28 d with no dose adjustment.

Patients at Children's Medical Center Dallas between ages 6 and 18 years with Type 1 diabetes within one week of diagnosis were eligible.
Diabetes care. At diagnosis, all subjects were placed on a basal-bolus insulin regimen with glargine and either lispro or aspart. For the duration of the study, insulin doses were adjusted per standard clinic protocol with target glucose of 80-140 mg/dL fasting and 80-180 mg/dL before meals. At each study visit, we recorded the subject's current insulin doses and weight to allow calculation of the total daily dose (units/kg/day).
Anakinra. After study enrollment, all subjects started anakinra (Kineret; Amgen, Thousand Oaks, CA) as a subcutaneous daily injection. Subjects weighing more than 25 kg at the time of enrollment received 100 mg daily whereas those weighing 25 kg or less received 50 mg daily. Anakinra was continued for a total of 28 days with no dose adjustment.

Anakinra

Sex: Female, Male

Ethnicity (NIH/OMB)

A1c (Median (IQR))

Beta hydroxybutyrate (mg/dL) (Median (IQR))

Total daily insulin dose at hospital discharge (U/kg/day) (Mean)

Initial IDAA1c (Median (IQR))

Expression data at baseline and after treatment were available on 10 patients who had received anakinra. These were compared to similarly-timed samples from 10 patients from control group B. Several attempts have been made to contact the PI to verify information, but were unsuccessful. Unable to verify if 10 or 12 patients were analyzed.

12 autoantibody positive subjects with newly diagnosed type 1 diabetes who were treated with anakinra

Effect of Anakinra Treatment on PBMC Gene Expression for Patients

Mixed-meal tolerance tests. MMTTs were conducted at the UT Southwestern Clinical Translational Research Center (CTRC). Subjects underwent MMTTs at 3-4 wk after diagnosis and again at 7 months after diagnosis. C-peptide analyses were performed by Dr Philip Raskin (UTSouthwestern MedicalCenter, Dallas, TX,USA). C-peptide AUC was calculated for each MMTT using the trapezoidal method. C-peptide AUC data between groups were rank transformed and then analyzed using a two-way repeated measures analysis of variance (ANOVA).

C-peptide Secretory Capacity

Patients at Children's Medical Center Dallas between ages 6 and 18 yr with type 1 diabetes within 1 wk of diagnosis were eligible. Exclusion criteria included treatment with systemic or inhaled corticosteroids or any other immunomodulatory drug, active infection, history of mycobacterial disease, pregnancy, live vaccine administration within 90 d of enrollment, and severe comorbidities. Patients were excluded if it was uncertain whether they had type 1 or type 2 diabetes.

Overall Study

Perrin White

Type 1 Diabetes Mellitus

Patients will receive daily anakinra therapy for 28 days

glutamic acid/gorączka

Stem Cell Transplantation for Sickle Cell Anemia

Anti-inflammatory Therapy With Anakinra in Newly Diagnosed Type 1 Diabetes

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