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Summary:Keywords: hematopoietic progenitors; microenvironmental progenitors; acute myelogenous leukemia; chemotherapy; LTC-IC; hematopoietic engraftment Since reduced marrow cellularity and prolonged pancytopenia following autologous bone marrow transplantation (ABMT) have been frequently observed in patients with acute myelogenous leukemia (AML)The structural integrity of the hematopoietic system is included in the AML10 GIMEMA/EORTC trial, the maintained by a relatively small population of selfquestion was raised to what extent hematopoietic and renewing stem cells which can differentiate to produce promicroenvironmental progenitor cells were involved in genitors committed to terminal maturation. 1 The developthese patients. Marrow hematopoietic progenitors were ment of hematopoietic cells in vivo occurs in intimate investigated by a short-term methylcellulose assay association with a heterogeneous population of mesenchyquantitating multipotent CFU-Mix, erythroid BFU-E mal, connective tissue type cells and their associated and granulocyte-macrophage CFU-GM, as well as a biosynthetic products, which constitute the stromal tissue long-term assay quantitating long-term cultureof the bone marrow. Stromal cells of the hematopoietic initiating cells (LTC-IC). The marrow microenviron-microenvironment include fibroblasts, endothelial cells, ment was studied by evaluating the incidence of fibroadipocytes, and macrophages. 2 Based on a number of studblastoid progenitors (CFU-F) and the capacity of stroies, 3 the existence of self-renewing stromal stem cells with mal layers to support allogeneic hematopoietic multilineage differentiation capacity and capable of generprogenitors. As compared to normal controls (n = 57), ating progenitors with restricted development potential, AML patients (n = 26) showed a statistically significant including fibroblast, osteoblast and chondrocyte progenireduction of the mean (± s.e.m.) number of CFU-Mix tors, has been hypothesized. 4-6(5.3 ± 0.6 vs 0.8 ± 0.2, P р 0.0001), BFU-E (68 ± 5 vs Standard-and high-dose therapies currently used for the 20 ± 4, P р 0.0001), CFU-GM (198 ± 11 vs 144 ± 15, P treatment of hematological and nonhematological malig-р 0.008), and LTC-IC (302 ± 46 vs 50 ± 8, P р 0.001).nancies induce transient or permanent damage of hematoThe mean (± s.e.m.) incidence of marrow CFU-F was poietic and stromal progenitor cell compartments. 7,8not significantly reduced as compared to normal conDespite such chemotherapy-induced defective progenitor trols (48 ± 6 vs 52 ± 7, P р 0.73). Seventeen AML strocell growth, the reinfusion of autologous marrow can reconmal layers were tested for their capacity to support the stitute the hematopoietic system, even in acute myelogengrowth of allogeneic hematopoietic progenitors. Seven ous leukemia (AML) patients treated with remission inducsamples failed to support any progenitor cell growth, tion regimens exerting a significant marrow toxicity. 9,10seven had a significantly lower supportive activity as Recently, therapeutic trials have been...

Summary: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 followup 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. Bone Marrow Transplantation (2000) 26, 1045-1049. Keywords: autologous stem cell transplantation; multiple myeloma; high-dose idarubicineThe combination of melphalan and prednisone has been the standard treatment for multiple myeloma (MM) for the past 30 years. The response rate is about 50%, with Ͻ10% of patients achieving a complete response and the median survival not exceeding 3 years. 1,2 Extensive trials of other drug combinations have not led to major improvements in clini- cal outcome, and multiple myeloma remains a fatal neoplasm due to the marked drug resistance of tumor cells to standard chemotherapy. [3][4][5][6] The use of high-dose therapy followed by stem cell support has demonstrated an increased incidence of complete remission (CR) in single-arm studies. 7-10 A recent study from the French group on 200 newly diagnosed MM patients has demonstrated the superiority of autologous transplantation vs standard chemotherapy in terms of response rate and survival. 11 Moreover, the wide use of peripheral blood-derived stem cell precursors, 12-15 which is associated with low transplant-related toxicity, has allowed this approach to be extended to patients up to 70 years of age, and has permitted the use of double or triple transplants with high-dose melphalan as conditioning. [16][17][18] Following the impressive results reported by De Witte and colleagues in the allogeneic and autologous transplant setting, [19][20][21][22] we chose to intensify the conditioning regimen by adding high-dose idarubicine...

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.

Thymoma is an uncommon slowly growing neoplasm. It usually presents with paraneoplastic syndromes including the immunodeficiency syndrome called Good syndrome and hematological disorders. Pure red cell aplasia is a well-recognized complication of thymoma, and aplastic anemia is very rare in association with GS. We report a case of GS in a heavily treated patient with stage IV thymoma associated with a pure red cell aplasia and an amegakaryocytic thrombocytopenia that evolved into an AA and provide an up-to-date review of the relevant literature. This is the first case of the association of GS and AA with the coexistence of a heavily treated stage IV thymoma. The fatal outcome was not related to the progression of the thymoma, but rather to the severe infectious complications. The combination of lymphopenia and hypogammaglobulinemia typical of GS, coupled to the neutropenia, caused by bone marrow failure, was the main predisposing factor for the unfavourable outcome.