Emmanuel Katsanis

Busulfan, fludarabine, and melphalan as hematopoietic cell transplant conditioning, was used in 6 patients aged 1 to 19 years with very high-risk myeloid malignancies. This dose regimen had an acceptable toxicity profile resulting in complete donor engraftment even following transplantation of small 2/6 antigen disparate umbilical cord blood grafts. It provided excellent disease control as all patients had high-risk features in terms of cytogenetics, therapy-related leukemia, and/or significant measurable disease before transplant. All patients remain in remission, without acute or chronic graft-versus-host disease with a median follow-up of 24 months. A larger study is indicated to confirm the efficacy and safety of this regimen.

Dendritic cells (DCs), essential for the initiation and regulation of adaptive immune responses, have been used as anticancer vaccines. DCs may also directly trigger tumor cell death. In the current study, we have investigated the tumoricidal and immunostimulatory activities of mouse bone marrow-derived DCs. Our results indicate that these cells acquire killing capabilities toward tumor cells only when activated with LPS or Pam3Cys-SK4. Using different transgenic mouse models including inducible NO synthase or GP91 knockout mice, we have further established that LPS- or Pam3Cys-SK4-activated DC killing activity involves peroxynitrites. Importantly, after killing of cancer cells, DCs are capable of engulfing dead tumor cell fragments and of presenting tumor Ags to specific T lymphocytes. Thus, upon specific stimulation, mouse bone marrow-derived DCs can directly kill tumor cells through a novel peroxynitrite-dependent mechanism and participate at virtually all levels of antitumor immune responses, which reinforces their interest in immunotherapy.

Relapse of acute lymphoblastic leukemia (ALL) in the breast is uncommon and often precedes systemic relapse, resulting in poor survival. We report the development of breast involvement of ALL in a 20-year-old woman 32 months after a related allogeneic peripheral blood hematopoietic cell transplantation (PBHCT) in first remission. This extramedullary relapse occurred in the continuous presence of complete donor chimerism. After systemic re-induction chemotherapy and a second PBHCT using donor cells that had been cryopreserved at first transplant, our patient has remained in second complete remission for more than 44 months.

While the role of T helper 17 lymphocytes (Th17) in the pathogenesis of autoimmune diseases and in infectious immunity has been relatively well defined, the impact of these cells and their associated cytokines on cancer development is still under debate. Although multiple reports have indicated that Th17 can promote anticancer immunity, others have argued that these cells may exhibit tumor-promoting properties. This dichotomy in the function of Th17 lymphocytes in cancer may be related to the versatile nature of these cells, being capable of differentiating into either proinflammatory Th1 or suppressive FoxP3-expressing Treg cells or hybrid T cell subsets depending on the underlying environmental conditions. In the current review, we examine the role of Th17 lymphocytes and Th17-associated cytokines in cancer and discuss how factors that control their final lineage commitment decision may influence the balance between their tumor-promoting versus tumor-suppressing properties.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cell that is exceptionally rare in the first five years of life, particularly as a secondary malignancy. This report describes a case of secondary CML in a four-year-old female occurring after AML treatment. Interestingly, CML developed while on immunosuppression for a heart transplant due to anthracycline-induced cardiomyopathy.