Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis.

A 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m2 and increased each month by 10 mg/m2. It was then administered by continuous infusion until June 2000, starting at 20 mg/m2/d and tapering by 5 mg/m2 every 2 weeks to a final daily dose of 5 mg/m2/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis.

Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients.

OBJECTIVES: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. METHODS: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG performance status < or = 3, HIV-negative and no prior treatment. Thirteen patients (1996-1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. RESULTS: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. CONCLUSIONS: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.

Aneurisma roto de arteria esplénica, seis años después de traumatismo abdominal / Ruptured aneurysm of the splenic artery six year after abdominal traumatism

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Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2-67) not responding to a first course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3.5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 microg/kg subcutaneously from day 1 to 90). The median interval between first and second treatment was 151 d (range 58-361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, defined as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14-377). Nine patients (30%) achieved complete remission (neutrophils >/=2.0 x 109/l, haemoglobin >/=11 g/dl and platelets >/=100 x 109/l). The overall survival rate was 93% with a median follow-up of 914 d (range 121-2278). So far, no patient has relapsed. Female gender was significantly associated with a poorer likelihood to respond (P = 0.0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to first-line IS treatment.

Hairy cell leukemia without splenomegaly nor myelofibrosis in a patient with gastric adenocarcinoma: early phase of the disease or a variant?

The first case of patient affected both by gastric carcinoma and hairy cell leukemia (HCL) is reported. From a clinical standpoint, this 54-year old man presented with striking leukopenia without splenomegaly. From a morphological point of view, the infiltration by leukemic cells occurred in the hypoplasic areas of the bone marrow biopsy (BMB) without increase in reticulin fibers. From these observations the authors deduce that: 1) BMB in many cases is the only morphologic tool for diagnosis and prognosis of HCL; 2) probably the "hypoplasic" variant of HCL will become more frequent, because of the increasing indication to BMB in course of pancytopenia, even in absence of splenomegaly; 3) our case is probably related more to an early phase of the disease than to a distinct variant. In addition, we propose that the co-existence of an aggressive solid tumor and HCL could be related to the immunosuppressive action by hairy cells.

[Monoclonal gammopathies: differential diagnosis with bone marrow biopsy]. / Le gammopatie monoclonali: diagnostica differenziale su biopsia osteomidollare.

Aim of the present study is to examine the morphological aspects of monoclonal gammopathies (GM) detectable by bone marrow biopsy. With reference to Multiple Myeloma (MM), the more important disease of this group from a clinical standpoint, other conditions will be later evaluated. Particular attention will be given to Monoclonal Gammopathy of Undetermined Significance (MGUS) that still today is characterized by wide shadows concerning both ethiology and evolution significance.

Multiple myeloma. New treatment options.

Before proceeding to treatment selection for multiple myeloma, it is important to exclude monoclonal gammopathy of unknown significance or any similar smouldering or indolent type of myeloma not requiring immediate chemotherapy. In patients with active myeloma, pretreatment prognostic classification is important for appropriate balancing of the risks and benefits of particular treatment options. For example, conventional chemotherapy such as melphalan/prednisone may be appropriate for an elderly patient with active stage III myeloma, whereas high dose chemotherapy with or without bone marrow transplantation or cytokine support may be considered for the patient under age 45 with even earlier stage disease. A variety of options are now available for patients with relapsing or resistant disease, particularly using agents with potential for reversal of multi-drug resistance. The use of interferon-alpha as maintenance following initial response to chemotherapy is important for prolongation of remission, duration and potentially survival. A variety of supportive measures are also helpful including the use of epoetin (erythropoietin) to improve refractory anaemia and bisphosphonates for the inhibition of ongoing bone resorption. With the availability of various treatment options, it has become important for patients to be evaluated by a specialist in the field.

Poor prognosis acute myeloid leukaemia treated by matched unrelated donor marrow transplant without preceding total body irradiation.

Two patients with acute myeloid leukaemia, one in relapse after autologous bone marrow transplantation (BMT) (aged 52 years) and the other with primary resistant disease secondary to previously treated malignancy, have received marrow transplants from matched unrelated donors. Cytoreductive conditioning in both cases was with high-dose combination chemotherapy alone. Engraftment was aided by the administration of total lymphoid irradiation together with in vivo antilymphocyte antibody prior to marrow infusion. Both patients survive in complete remission, currently at 12 and 15 months post-BMT respectively. The avoidance of total body irradiation in BMT patients at high risk of early treatment-related mortality may be advantageous.