GEMTUZUMAB OZOGAMICIN COMBINED WITH INDUCTION CHEMOTHERAPY IN YOUNG ADULTS WITH ACUTE MYELOID LEUKEMIA: REVIEW AND PERSPECTIVES.

Progress in treatment of acute myeloid leukemia (AML) is slow. Many new agents have been tested, but few were approved. Gemtuzumab Ozogamicin (GO) is a new AML-targeted drug that is composed by a monoclonal antibody targeting a surface antigen of myeloid leukemic cells (CD33) combined with a potent cytotoxic (calicheamicin). We review here the studies of GO in AML, including an update of the Italian studies, and we trace back the story of a drug that was developed 15 years ago and, regrettably, is no longer available for the treatment of AML, with the exception of Japan. GO was approved by the US FDA for the second-line treatment of AML in the elderly, and was shown by several European large prospective and randomized studies to be active also in first line, both alone, but particularly in combination with standard chemotherapy. Regrettably, a registration study that was performed in US could not confirm the superiority of GO and chemotherapy on chemotherapy alone, and the drug was withdrawn. The differences among the US and the European studies are discussed. The profile of the AML patients who are expected to benefit more by the reintroduction of GO is proposed: first-line, less than 60 years old, CD33 expressed in more than 20% leukemic cells, low/intermediate cytogenetic risk, and low expression of the PGP multidrug resistance protein

Fusobacterium nucleatum: a rare cause of bacteremia in neutropenic patients with leukemia and lymphoma

Although anaerobic bacteremias are uncommon in oncohematologic patients, nevertheless they have been considered an emergent problem in the last few years. Fusobacterium nucleatum is an anaerobic Gram-negative bacillus commonly present in the oral cavity and in the respiratory and genito-urinary tracts. Over a 10-year period 18 episodes of F. nucleatum bacteremia in patients with hematological malignances (15 leukemias and 3 lymphomas) have been observed in our Department of Hematology. Predisposing factors included oropharyngeal mucositis and severe neutropenia owing to intensive chemotherapy. In our experience no septic shock occurred and the outcome of bacteremias caused by F. nucleatum was favorable

The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia

JAK-2 inhibitors and allogeneic transplant in myelofibrosis

7The activation of the JAK1/JAK2 pathway plays a crucial role in the pathogenesis of myelofibrosis. Treatment with the JAK2 inhibitor ruxolitinib demonstrated to reduce splenomegaly and symptoms in patients affected by myelofibrosis, leading to a significant improvement of overall survival in comparison with the supportive therapies. Taking in account this recent therapeutic progress, it is necessary to redefine the role of the allogeneic hematopoietic stem cell transplantation, which has been considered the only curative option for fit myelofibrosis patients up to now. In the era of JAK2 inhibitors, allogeneic transplant is still indicated in patients with intermediate-2 and high-risk myelofibrosis or red blood cell transfusion dependent patients or patients with unfavourable karyotype. There is no direct evidence to recommend which conditioning regimen should be preferentially adopted. Graft failure, relapse and transplant related mortality are still current issues of the allogeneic stem cell transplantation, particularly from unrelated donors. Ruxolitinib can be efficaciously included in the platform of allogeneic transplant. In fact, ruxolitinib treatment for 3-4 months before transplant has demonstrated to reduce spleen and improve performance status in about 30-50% of patients, without impairing the outcome of the subsequent transplant. Ruxolitinib has to stopped the day before conditioning to avoid rebound phenomenon. There are no sufficient data to recommend ruxolitinib administration after transplant with the aim of eradicating minimal residual disease and preventing relapse.openopenPatriarca, F; Sperotto, A; De Marchi, R; Perali, G; Cigana, C; Lazzarotto, D; Fanin, RPatriarca, Francesca; Sperotto, A; De Marchi, R; Perali, G; Cigana, C; Lazzarotto, D; Fanin, Renat