Reduced-intensity conditioning has extended the use of allogeneic hematopoietic stem cell transplantation (HSCT) to patients otherwise not eligible for this treatment due to older age or frailty. One hundred twelve acute myelogenous leukemia/myelodysplastic syndromes patients received fludarabine and melphalan (FM) conditioning with allogeneic HSCT. Most patients (73%) were not in remission. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini-methotrexate. Median age was 55 years (range, 22-74). Donors were related (53%) and unrelated (47%). Median follow-up of surviving patients (n = 43) was 29.4 months (range, 13.1-87.7). The complete remission (CR) rate was 82%. Estimates of 2-year survival were 66%, 40%, and 23% for patients in CR, with active disease without and with circulating blasts at HSCT, respectively. In multivariate analysis, survival was negatively influenced by active disease at HSCT and development of grade II-IV acute GVHD. Presence of circulating blasts at HSCT negatively influenced freedom from disease progression. Incidence of nonrelapse mortality (NRM) was significantly higher for patients with active disease, but was not influenced by patient age. Patients in CR had a day-100 and 2-year NRM of 0% and 20%, respectively. Use of unrelated donors increased the risk of NRM only among patients with active disease. FM and HSCT elicited long-term disease control in a significant fraction of this high-risk cohort.

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The treatment of steroid-refractory acute graft-versus-host disease (aGVHD) remains a clinical challenge, for which no standard therapy exists. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) that has been successfully used as part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) to prevent GVHD. The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (>or=grade II) following HSCT. Eighteen patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days. Response was assessed at day 28 following initiation of alemtuzumab. Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV. The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3. Fifteen patients (83%) responded to alemtuzumab, including 6 (33%) with complete response. All 3 unresponsive patients died of GVHD. Ten of 15 responders are alive at median follow-up of 11 months (range: 3-24). Infections occurred in 14 patients, including cytomegalovirus (CMV) reactivation in 11. Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively. Alemtuzumab was well tolerated, and induces promising response rates in steroid-refractory aGVHD.

Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n ‫؍‬ 30), 1 antigen-mismatched related (n ‫؍‬ 4), or matched unrelated (n ‫؍‬ 30). With median follow-up of 7 years, overall survival (OS) and progressionfree survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronicphase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time. (Blood. 2007; 110:3456-3462)

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The molecular basis of chronic idiopathic myelofibrosis (CIMF) has remained elusive, thus hampering the development of effective targeted therapies. However, significant progress regarding the molecular mechanisms involved in the pathogenesis of this disease has been made in recent years that will likely provide ample opportunity for the investigation of novel therapeutic approaches. At the forefront of these advances is the discovery that 35%-55% of patients with CIMF harbor mutations in the Janus kinase 2 tyrosine kinase gene. Until very recently, the management of patients with CIMF involved the use of supportive measures, including growth factors, transfusions, or interferon, and the administration of cytoreductive agents, such as hydroxyurea and anagrelide. However, several trials have demonstrated the efficacy of antiangiogenic agents alone or in combination with corticosteroids. In addition, the use of reduced-intensity conditioning allogeneic stem cell transplantation has resulted in prolonged survival and lower transplantrelated mortality. The Oncologist 2006;11:929-943

BACKGROUND: The frequency of various subtypes of non-Hodgkin’s lymphoma (NHL) differs in various regions worldwide. OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin’s lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms. METHODS: According to the new WHO classification, a total of 1014 cases of non-Hodgkin’s lymphoma diagnosed during the period 2002–2006 were reviewed and reappraised with their morphological, immunological and clinical characteristics in one general hospital from Lima, Peru. All cases corresponded >18 years old. RESULTS: There were 535 males and 479 females, mean age was 62.1 years (range 18 – 97 years) and the median was 64 years. B-cell neoplasms accounted for 763 cases (75.2%) and T/NK-cell neoplasms for 189 (18.6%). Sixty two cases (6.1%) were not classified. It was seen compared to that in the other Asian countries. Indolent lymphomas accounted for 17%, and aggressive ones for 83%. Among indolent lymphomas follicular grade I and II were the most common subset while MALT was second with low frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype, and accounted for 58.8% of all B cell lymphomas. Mantle and Burkitt lymphoma were very low incidence. Among the T cell lymphomas, peripheral T cell lymphomas, mycosis fungoides, Adult T Lymphoma/Leukemia (ATLL), T/NK nasal type Lymphoma were the most common subtypes. Nodal NHL occurred in 52% and extranodal in 48% of the cases. The more common extranodal presentation was stomach (14.1%), skin (8.1%), small intestine (2.9%) and nose (2.3%) CONCLUSIONS: The high incidence of T cell lymphomas, extranodal presentation and reduced frequency of indolent lymphoma in the current study is comparable to that reported from Asian countries.

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