Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies

The prognosis of pediatric patients with hematologic malignancies whose disease is primarily
refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely
poor. When new agents or chemotherapeutic regimens are unable to induce remission in this
patient population, hematopoietic stem cell transplant (HSCT) is also a poor alternative.
Thus, in this very high risk group, additional attempts at remission induction with various
combinations of chemotherapy alone will unlikely improve outcome and will contribute to
overall toxicity. Alternative therapies are needed in these patients with chemotherapy
resistant disease.

Immunotherapy with natural killer (NK) cell infusion has the potential to decrease toxicity
and induce hematologic remission. NK cells can kill target cells, including leukemia cells,
without prior exposure to those cells. In patients undergoing allogeneic HSCT, several
studies have demonstrated the powerful effect of NK cells against leukemia. Furthermore, NK
cell infusions in patients with primary refractory or multiple-relapsed leukemia have been
shown to be well tolerated and void of graft-versus-host disease effects. In this high risk
group, complete leukemic remission has been observed in several of these patients after NK
cell infusion.

With the current technology available at St. Jude, we have developed a procedure to purify
NK cells from adult donors. This protocol will assess the safety of chemotherapy and IL-2
administration to facilitate transient NK-cell engraftment in research participants who have
chemotherapy refractory hematologic malignancies including acute lymphoblastic leukemia,
chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, or
non-Hodgkin's lymphoma. In this same cohort, we will also intend to explore the efficacy of
NK cells infused in those participants who have chemotherapy refractory disease.