Splenic marginal zone lymphoma in a HIV-1 infected patient: evidence favouring a pathogenetic role of HIV-1 itself in the lymphomagenesis.

A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.

[Budd-Chiari syndrome and splanchnic vein thrombosis: masked myeloproliferative neoplasms and JAK2V617F]. / Sindrome di Budd-Chiari e trombosi delle vene splancniche: neoplasie mieloproliferative mascherate e mutazione di JAK2V617F.

The Budd-Chiari Syndrome (BCS) and the splanchnic vein thrombosis are characterized by hepatic venous outflow obstruction, generally due to venous thrombosis. These rare diseases are usually caused by multiple concurrent factors, including acquired and inherited thrombophilias. Since the diagnosis of myeloproliferative neoplasms (MPNs) is often difficult in patients with BCS and splanchnic vein thrombosis because of spleen enlargement, secondary pancytopenia and bleeding disorders, recent observations have included in the diagnostic work-up the analysis of the JAK2 mutation. The revision of several recent reports clarify the importance of the JAK2V617F detection in the diagnostic work-up of the BCS and splanchnic vein thrombosis, allowing the demonstration of masked MPNs among these cases that may benefit, in the near future, of target molecular therapies directed toward the JAK2 mutation.

[Therapeutic advances in neoplastic hematology: target therapy anti-CD33]. / Approcci terapeutici innovativi in oncoematologia: terapia mirata anti-CD33.

Antibodies capable to recognize antigen expressed on cancer cells represents the ideal approach for targeted anti neoplastic therapies. The CD33 antigen is present on 90% of acute myeloid leukemia blasts and is shared on normal hemopoietic cells only on the non stem dillerentiating fraction. Gemtuzumab Ozogamicin (GO) is an engineered humanized antibody anti-CD33 conjugated with a potent intercalating agent, named calicheamicin, which is release only at intracellular level (lower pH), following a selective binding to CD33-positive cells, thus representing a promising approach for target anti-leukemia therapy. GO was approved conditionally by the Federal Drug Administration in May 2000 as a single therapy for first recurrence of Acute Myeloid Leukemia (AML) in a subset of older patients. Since 2000, treatment trials and pilot studies have revealed potential expanded applications along with potential limitations. Phase II trials have confirmed the activity and the efficacy of GO as single agent in the treatment of relapsed AML. More recently, clinical trials on induction and post-remission treatment of adult AML have shown efficacy of GO in combination chemotherapy. The strong and homogeneous CD33 expression in Acute Promyelocytic Leukemia (APL), have resulted in an effective treatment of this disease with GO used as salvage treatment, as well as innovative approach for molecular relapsed patients. However, the incidence of veno-occlusive disease, better defined as sinusoidal occlusive syndrome (SOS), must be taken into account as potential complication associated with the GO administration, especially in patients treated with ablative regimens. In conclusion, the extension of the approval in Italy to AML CD33+ in relapsed, regardless age limitation, along with the ongoing evaluation by the European EMEA, represent the basis for a large clinical application of GO in myeloid malignancies potentially extended to paediatric patients with AML and to ALL CD33+.

High-dose idarubicine, busulphan and melphalan as conditioning for autologous blood stem cell transplantation in multiple myeloma. A feasibility study.

Extensive studies have tested the clinical impact of double and triple sequential transplants as front-line therapy in MM, following the suggestion that dose escalation can overcome the marked drug resistance characteristic of this disease, but the superiority of such approaches vs one single transplant has still to be demonstrated. The aim of our study was to evaluate the feasibility and efficacy of high-dose idarubicine intensification of a standard busulphan-melphalan conditioning regimen in MM. Twenty-eight patients (median age 55 years) with sensitive disease received PBSCT after high-dose idarubicine combined with busulphan and melphalan and followed by s.c. rhG-CSF until PMN recovery. The most severe toxicity was represented by oral mucositis which resolved with hemopoietic reconstitution. Overall response and CR rate were 52% and 40%, respectively. Currently, 36 patients are alive and 19 are progression-free a median of 20 months (12-36) from transplant. The 3-year projected probability of progression-free survival for patients transplanted after first-line treatment is 60%. The combination of Ida/Bu/Melph appears a promising alternative regimen for PBSCT in myeloma, with low transplant-related toxicity and fast hematological recovery. Long-term follow-up and a prospective randomized study, now ongoing, will probably clarify whether an idarubicine-intensified regimen will result in superior outcomes to conventional conditioning and even be comparable to a double consecutive transplant program.

Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors.

Since reduced marrow cellularity and prolonged pancytopenia following autologous bone marrow transplantation (ABMT) have been frequently observed in patients with acute myelogenous leukemia (AML) included in the AML10 GIMEMA/EORTC trial, the question was raised to what extent hematopoietic and microenvironmental progenitor cells were involved in these patients. Marrow hematopoietic progenitors were investigated by a short-term methylcellulose assay quantitating multipotent CFU-Mix, erythroid BFU-E and granulocyte-macrophage CFU-GM, as well as a long-term assay quantitating long-term culture-initiating cells (LTC-IC). The marrow microenvironment was studied by evaluating the incidence of fibroblastoid progenitors (CFU-F) and the capacity of stromal layers to support allogeneic hematopoietic progenitors. As compared to normal controls (n = 57), AML patients (n = 26) showed a statistically significant reduction of the mean (+/-s.e.m.) number of CFU-Mix (5.3 +/- 0.6 vs 0.8 +/- 0.2, P < or = 0.0001), BFU-E (68 +/- 5 vs 20 +/- 4, P < or = 0.0001), CFU-GM (198 +/- 11 vs 144 +/- 15, P < or = 0.008), and LTC-IC (302 +/- 46 vs 50 +/- 8, P < or = 0.001). The mean (+/-s.e.m.) incidence of marrow CFU-F was not significantly reduced as compared to normal controls (48 +/- 6 vs 52 +/- 7, P < or = 0.73). Seventeen AML stromal layers were tested for their capacity to support the growth of allogeneic hematopoietic progenitors. Seven samples failed to support any progenitor cell growth, seven had a significantly lower supportive activity as compared to normal stromal layers (13 +/- 5 vs 249 +/- 56, P < or = 0.002), whereas three cultures could not be analyzed due to contamination. In conclusion, induction and consolidation regimens used in AML patients of the AML10 protocol induce a markedly defective in vitro growth of primitive hematopoietic progenitors and a severe functional defect of marrow stroma. The association of hematopoietic with microenvironmental damage might play a key role in the delayed hematopoietic regeneration observed following ABMT in patients of the AML10 trial.