Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Decisional Algorithm to Start Iron Chelation in Minimally Transfused Young Beta-thalassemia Major Patients Naive to Iron Chelation Therapy. A Comparative Randomized Prospective Study
Brief Summary: A prospective randomized study on Safety, Tolerability and Efficacy of oral Low dose DFP (50 mg/kg/day) in minimally transfused B-TM after 5 transfusions when SF reaches 500 ng/m and with either appearance of LPI \> 0.2 or TSAT reaches 50% compared with non treatment arm.

So the aim of this study:

1. To determine the time as well as amount of transfused iron ( calculated in mg iron/kg ) which lead to Serum ferritin reaches 500 ng /ml and LPI appearance \>0.2 as well as TSAT reaches 50 % .
2. Tolerability and safety of early low dose DFP 50mg/kg and effectiveness to postpone or prevent SF from reaching 1000 ng/ml or LPI \>0.6 or TSAT \>70% in comparison to patients not starting chelation therapy
3. Determine adverse events whether drug or non drug related


Options:
A: Inclusion Criteria:

* Subjects with transfusional iron overload secondary to thalassemia major , sickle cell disease showing up-trend in SF aged 6 Years or older, may participate after Approval of Ethical committee giving written informed consent.
* Subjects must have a serum ferritin greater than \>2500 ng/mL, a platelet count greater than 100,000/mm3, and a serum creatinine within the normal range.
* A woman of childbearing potential must have a negative serum pregnancy test at screening. She must use a medically acceptable form of birth control during the study and for 1 month afterward.
* The subjects must also have a level of understanding and willingness to cooperate with the confinement and procedures described in the consent form and scheduled by the study site. In addition, he/she must be able to provide voluntary written informed consent.

Exclusion Criteria:

* Subjects with a past history of agranulocytosis, history of clinically significant gastrointestinal, renal, hepatic ALT \> 10 times high normal, OR \> 50% increase of serum creatinine from basal value, pulmonary or cardiovascular disease. Patients with a history of tuberculosis, epilepsy, psychosis, glaucoma or any other condition, which in the opinion of the investigators, would jeopardize the safety of the subject or impact the validity of the study results.
* Subjects with HIV positive or have active HCV.
* A history of serious immunologic hypersensitivity to any medication, such as anaphylaxis or angioedema.
* Participation in a previous investigational drug study within the 30 days preceding screening..
* Women who are pregnant, or breast-feeding.
* Current alcohol or drug abuse.
* An inability to adhere to the designated procedures and restrictions of this protocol.
* Subjects receiving warfarin, digoxin, or anti-arrhythmic or anti-seizure medications.
* Subjects with a known allergy to Exjade or DFP that prevents chronic administration.
B: Inclusion Criteria:

* Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml
* Patients of either gender and aged ≥ 2 years
* Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.

Additional Inclusion Criteria for Adult Patients:

* Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

* The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.

Exclusion Criteria:

* Non-transfusional hemosiderosis
* Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
* Patients with mean levels of alanine aminotransferase (ALT) \> 300 U/l
* Patients with uncontrolled systemic hypertension
* Patients with serum creatinine above the upper limit of normal (ULN)
* Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is \> 0.5 (mg/mg) and one is ≤ 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is \> 0.5 (mg/mg) in two of the three determinations are also to be excluded.
* History of nephrotic syndrome
* Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
* Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
* Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
* Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
* Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

  * history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
  * history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  * history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
  * history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
  * history of urinary obstruction or difficulty in voiding.
* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
* Patients with positive test to HIV
* Life expectancy of \< 1 year

Exclusion Criteria for Pediatric Patients:

* Patient body weight which prevents the use of the smallest tablet strength (i.e. 125 mg) for proper dosing

Other protocol-defined inclusion/exclusion criteria may apply.
C: Inclusion Criteria:

* Beta-thalassemia patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
* Liver iron content greater than 2 mg iron/g dw as measured by liver biopsy
* Need for regular transfusions 8 or more times per year

Exclusion Criteria:

* Non-transfusional iron overload or transfusion-dependent anemias other than beta-thalassemia.
* Documented toxicity to deferoxamine
* Elevated liver enzymes in the year preceeding enrollment
* Active hepatitis B or hepatitis C
* HIV seropositivity
* Elevated serum creatinine or significant proteinuria
* History of nephrotic syndrome
* Uncontrolled systemic hypertension
* Fever and other signs/symptoms of infection within 10 days prior to start of the study
* Presence of clinically relevant cataract or previous history of clinically relevant ocular toxicity related to iron chelation
* Second or third degree AV block, clinically relevant Q-T interval prolongation, or patients requiring digoxin or other drugs that prolong the Q-T interval
* Diseases (cardiovascular, renal, hepatic, etc.)that would prevent the patient from undergoing any of the treatment options
* Psychiatric or additive disorders that would prevent the patient from giving informed consent
* History of drug or alcohol abuse within the 12 months prior to the study
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within 4 weeks or topical investigational drugs within 7 days before the start of the study
* Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as gastrointestinal disease or major surgery, renal disease, difficulty voiding or urinary obstruction, or impaired pancreatic function.
* Non-compliant or unreliable patients.
* Patients unable to undergo any study procedures such as the hearing or eye tests, or the liver echocardiography.
* Inability to undergo a liver biopsy.
* Patients that would need a dose of ICL670 less than 125 mg per day.
D: Inclusion Criteria:

1. Young beta thalassemia major patients (diagnosed by HPLC, CBC) who started transfusion therapy who received 5-7transfusions or less, aged more than 6 months.
2. Pre-transfusional Hb should be \>9 g/dL.
3. Serum ferritin should be ≤ 500ng/ml, transferrin saturation ≤ 50%.

Exclusion Criteria:

* 1. Beta thalassemia intermedia patients, patients with other transfusion dependent anemias (myelodysplasia, other chronic hemolytic anemias , pure red cell aplasia , aplastic anemia ) 2. Patients with levels of ALT \>5 the upper limit of normal (ULN), serum creatinine \> ULN on 2 measurements.

  3. Patients with history of agranulocytosis \[absolute neutrophil count (ANC) \<0.5×109/L\].

  4. Non complaint patients acknowledged by reviewing the patient's records.

Answer: D