Patients receiving haplo-SCT are at high-risk of relapse. Vγ9Vδ2 T cells exhibit is a well-known population able to exert cytotoxicity toward a large range of tumor in vitro or in vivo. Activating and expanding Vγ9Vδ2 T cells early after haplo-SCT by using a combination of Zoledronic acid and low-dose interleukine (IL) -2 may be of benefit for patients by reducing incidence of relapse. The optimal dose of IL-2 to use remains to be determined.

This will be a Phase 1 3+3 escalation study. Three to 15 patients are planned. It will be proposed to Patients who refuse to participate to have samples collected until day +70 to study immune and gamma/delta T cells reconstitutions after haplo-transplant.

Zoledronic acid will be administered as a single dose according to marketing and regulatory authorization at the dose of 4 mg over 15 min intravenously at day+15 post-transplant. Zoledronic acid infusion must be stopped in case of grade 3/4 adverse events during infusion.

IL-2 will be administered at a unique low-dose level 5 days per week for 4 consecutive weeks from Monday to Friday subcutaneously . IL-2 has already marketing authorization for various indications.

Three IL2 levels will be tested:

Level 1: 2 millions UI/Infusion Level 2: 4 millions UI/Infusion Level 3: 6 millions UI/Infusion Zoledronic acid and IL2 have to start at day+15 if it is a Monday or the first Monday following day+15 in order to avoid administration on week-end.

Inclusion Criteria:

• Age: 18-70 years old
• Patients with a hematological disease eligible for a haplo-SCT using the Baltimore regimen as conditioning regimen (Luznik, BBMT, 2008) (See 5.1.2)
• Patients with no HLA matched sibling or unrelated donors
• ECOG <=2
• Signed informed consent
• Patient affiliated to or beneficiary of the National Health Service
• Patients previously transplanted are eligible to the study

Exclusion Criteria:

• Patients with a HLA matched sibling or unrelated donor
• Active uncontrolled infections
• HIV positive, active Hepatitis B or C
• Childbearing or child-breastfeading women
• Women or men without effective contraceptive barrier if needed
• Left ventricular ejection fraction < 50% with no previous severe cardiopathy
• Respiratory insufficiency defined as DLCO <40% of the corrected value
• Creatinine clearance <50 ml/min
• Serum bilirubin >2.5 or transaminases >5 fold of normal value except if due to the hematological disease
• Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Participation at the same time in another study in which investigational drugs are used
• Absence of written informed consent
• Contra-indication to Zoledronic acid: known hypersensitivity to Zoledronic acid or other bisphosphonate or Zoledronic acid formulation (excipients)
• Recent or programmed dental care
• Contra-indication to IL-2: known hypersensitivity to IL-2 or IL-2 formulation (excipients)
• No previous ou current use of zoledronic acid