Haploidentical Stem Cell Transplantation for Children With Therapy Resistant Leukemia

Inclusion criteria

Target population

• Refractory acute lymphoblastic leukemia

• Chemoresistant isolated or combined bone marrow relapse

• Relapse after during/after conventional treatment
• Relapse ≥6 months after allogeneic stem cell transplantation
• Primary induction failure
• Isolated extramedullary relapse after previous HSCT (>6 months)
• Refractory acute myeloblastic leukemia including sAML

• Chemoresistant relapse

• Relapse after during/after conventional treatment
• Relapse ≥6 months after allogeneic stem cell transplantation
• Primary induction failure

Inclusion criteria

to start induction treatment with multidrug regimen

• Age ≥ 1 and ≤21 years
• Patients with previous HCST ≥ 6 m
• Provide signed written informed consent patients', and patients' parents /guardians

• Older children should be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent as well.
• Cardiac output SF ≥25%
• Have adequate renal and hepatic functions as indicated by the following laboratory values:

• Calculated creatinine clearance ≥90 ml/min/1.73 m2
• Serum bilirubin ≤1.5 X upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
• Alkaline phosphatase ≤ 2.5 X ULN
• Performance score of ≥70% (Lansky or Karnofsky)
• A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Inclusion criteria

to proceed to transplant after induction

• Cardiac output SF ≥25%
• Have adequate renal and hepatic functions as indicated by the following laboratory values:

• Calculated creatinine clearance ≥90 ml/min/1.73 m2
• Serum bilirubin ≤1.5 X upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
• Alkaline phosphatase ≤ 2.5 X ULN
• Performance score of ≥70% (Lansky or Karnofsky)
• A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion criteria

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea.

The patient must have recovered from all acute toxicities from any previous therapy.

• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Pregnant or lactating patients.
• Any significant concurrent malignant disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.