Autologous Cytokine Induced Killer Cells (CIK) for Chronic Myeloid Leukemia (CML) Patients on Standard Drug Therapy

Patients with CML falls into various groups based on their disease stage and response to kinase inhibitors. In the context of currently available kinase inhibitors, allogeneic transplant and the various available new drug trials, there are still some patients who will not achieve a satisfactory or sustainable response. For such patients, we aim to employ CIK cell as an immunotherapeutic modality concurrent with their original CML-specific therapy. This will enable us to explore any additional activity of CIK cells against CML without any compromise to their ongoing, established treatment.

The following groups of patients are potential candidates:

• Blast crisis / accelerated phase patients who have failed to response to the kinase inhibitors but are fit to undergo induction chemotherapy as for the acute leukemia. Repeated cycles of CIK will be given in phase with the planned chemotherapy cycles, to observe for achievement of any remission and its durability.
• Blast crisis / accelerated phase patients who have achieved a haematological or cytogenetic response to the kinase inhibitors, but do not have further definitive curative options eg allogeneic transplant. In the absence of long term data with Dasatinib or Nilotinib , it is justifiable to study the efficacy of addition of CIK therapy to their baseline best response achievable with drug therapy.
• Patients with resistance to the currently available kinase inhibitors due to T315I mutation or other undefined mutations, with progressive relapse either at molecular, cytogenetic or haematological level, and do not have transplant as a curative option. In this group of patients additional of CIK to current treatment will show any activity of CIK against the drug-resistant mutant CML cells.
• Patients who have achieved a stable but residual molecular evidence of CML, who are willing to explore additional means with a hope to eradication of MRD. Since the role of immunotherapy is most relevant in MRD, CIK infusion will provide the proof of principal observation of whether imatinib-resistant CML Philadelphia stem cells can be eradicated by these ex vivo activated and expanded cytotoxic T cells.

Inclusion criteria

• Blast crisis / accelerated phase patients who have failed to response to the kinase inhibitors but are fit to undergo induction chemotherapy as for the acute leukemia.
• Blast crisis / accelerated phase patients who have achieved a haematological or cytogenetic response to the kinase inhibitors, but do not have further definitive curative options
• Patients with resistance to genetic or haematological level, and do not have transplant as a curative option.
• Patients who have achieved a stable but residual molecular evidence of CML, who are willing to explore additional means with a hope to eradication of MRD.

Patients must understand the trial nature of this study and the additional leukapheresis procedure needed for harvesting mononuclear cells.

Exclusion criteria

On recruitment :

• Renal impairment with Cr >200mmol/uL
• Liver impairment with transaminase >5x upper limit which is not due to disease
• Limited life expectancy <3 months

On day of infusion

• uncontrolled infection or significant bleeding
• unstable vital signs
• any degree of hypoxia requiring oxygen therapy.