Standardization of regimens in Narrowband UVB and PUVA in early stage mycosis fungoides: position paper from the Italian Task Force for Cutaneous Lymphomas.

UV-based (PUVA and narrowband UVB) phototherapy is broadly and commonly used in the treatment of Cutaneous T-cell Lymphomas (CTCL), yet unfortunately, the evidence for the efficacy of these treatments is based only on case series or prospective but non-randomized studies. Therefore, no internationally approved guidelines exist and no standardization of schedules has been proposed. Recently, consensus guidelines have been published by the United States Cutaneous Lymphoma Consortium. The aim of this study was to review the biological and clinical evidences on PUVA and NB-UVB in CTCL and to critically evaluate acceptability and feasibility of these guidelines in the real-life setting from the perspective of the Cutaneous Lymphoma Task Force of the Italian Lymphoma Foundation (Fondazione Italiana Linfomi, FIL).

Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy.

BACKGROUND: Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. OBJECTIVES: To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. METHODS: Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. RESULTS: In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. CONCLUSIONS: Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.

Combination treatment in CTCL: the current role of bexarotene.

Primary cutaneous T-cell lymphomas are a heterogeneous group of extranodal NH lymphomas primarily presenting in the skin without extracutaneos involvement at diagnosis. Treatment choices closely depend on clinic-pathologic entity and disease stage. Among available choices, oral bexarotene has shown efficacy and safety both in monotherapy and in association with other treatments, by virtue of its versatility and high synergism with alpha-interferon, photochemotherapy (PUVA), and chemotherapy. Moreover, when associated with a wise management of its side effects, bexarotene is well tolerated if used in long-term administration, and it is therefore a good candidate to maintenance treatment after different induction therapies. Recently, the Gruppo Italiano Linfomi Cutanei (GILC) has started some pilot studies, with the aim to investigate bexarotene potential in association with PUVA and single agent chemotherapy (as pegylated liposomal doxorubicin and gemcitabine), and as consolidation/maintenance treatment. The preliminary results of GILC pilot studies confirm the good tolerability and safety of low-intermediate dose bexarotene, and its potential synergism with PUVA and chemotherapy. In addition, its use in consolidation/maintenance has proven efficacy in improving overall response rate.

Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Acute promyelocyte leukemia arose from CALR 1 mutated post essential thrombocythemia- myelofibrosis with splanchnic vein thrombosis: A case report.

Major disease complications for patients with essential thrombocythemia (ET) include thrombosis and fibrotic or leukemic transformation. Calreticulin (CALR) mutation type 1 frequencies in ET are estimated between 7% and 11% and ET patients carrying CALR type 1 mutation are associated with lower risk of thrombosis but higher risk of myelofibrosis transformation compared to ET patients with JAK2 mutation. Leukemic transformation rates at 20 years are estimated at less than 5% for ET and risk factors for leukemic transformation are advanced age, thrombosis history, leukocytosis, and anemia. Amongst the subtypes of blast phase myeloproliferative neoplasms, acute promyelocytic leukemia is extremely rare. Herein, we present a case of a promyelocytic blast crisis of post-ET myelofibrosis with associated life-threatening splanchnic vein thrombosis. This case suggests that inflammation plays a key role in thrombotic events and fibrotic/leukemic transformation in ET patients, regardless the molecular landscape.

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase.

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNalpha, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC) <10 x 10[9]/l which was induced by the pretreatment with hydroxyurea. One patient completed the 12th course of ATRA maintaining WBC <10 x 10(9)/l, platelets <500 x 10(9)/l and spleen not palpable. The treatment with ATRA was well tolerated and only one patient discontinued the therapy because of non-hematological side-effects. The area under the concentration-time curve (AUC) decreased significantly (P< 0.001) during the first week of therapy. By adopting an intermittent dosing regimen, 1 week on/ 1 week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs equivalent to the ones achieved on day 1 of course 1. In conclusion, our results showed that ATRA alone appeared to be unable to control the WBC expansion in the CML patients in chronic phase. Moreover, it did not induce any remarkable cytoreductive effects on the platelet count and on the hemoglobin level. The major interest of ATRA would be in combination with other therapies. If ATRA was given in combination with IFNalpha or other agents, dose reduction of these would not be planned. On the basis of the pharmacokinetic profile, ATRA should be administered intermittently rather than continuously.

Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.

BACKGROUND: The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients. METHODS: We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented. RESULTS: Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years. CONCLUSIONS: Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF.

Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36. 2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P = 0. 0001; odds ratio 3.4) and >5 days on ANC <100/microl (P = 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC <100/microl affected infection outcome (P = 0.0024) whereas the antibiotic regimen did not. After day +30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0. 8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Gram-positive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.

Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides.

BACKGROUND/AIMS: CD8+ T cells and epidermal/dermal dendritic cells expressing CD1a are found among neoplastic CD4+ T cells in mycosis fungoides (MF) lesions. This study analysed the relation of CD8+ tumour infiltrating lymphocytes (TILs), CD1a+ epidermal Langerhan's cells (LCs), and dermal dendritic cells (DDCs) to clinicopathological parameters in 46 MF cases. METHODS: Pretreatment diagnostic biopsy specimens of 46 MF cases were submitted to histological analysis and immunohistochemistry. Four histological grades were defined based on the density of the neoplastic infiltrate: grade 1 (mild superficial perivascular infiltrate), grade 2 (moderate superficial perivascular infiltrate with some tendency to confluence), grade 3 (pronounced superficial band-like infiltrate), and grade 4 (deep nodular infiltrate). Epidermotropism was scored as low, moderate, or high. Numbers of CD8+ T cells and of dermal and epidermal CD1a+ cells were scored as 1 (low), 2 (moderate), and 3 (high). Correlations between these parameters and clinical data (age, sex, clinical type of lesions, stage, response to treatment, and recurrence) were analysed by the chi(2) test. RESULTS: Numbers of TILs and DDCs were associated with subepidermal infiltrates, being lower in less dense infiltrates, whereas there was no association between epidermal CD1a+ cells and the analysed parameters. Complete remission in treated patients was related to subepidermal infiltrates but not to TILs, LCs, or DDCs. CONCLUSIONS: These results support the notion that CD8+ cells and dermal CD1a+ cells are active against tumour cells. MF with low numbers of TILs could represent an early stage of the disease, before TILs are activated against tumour specific antigens.

Expression of c-myb and B-myb oncogenes on myelofibrotic marrow fibroblasts.

The term IMF (Idiopathic Myelofibrosis) refers to a primary bone marrow disease in which the normal haematopoietic bone marrow cells are for unknown reasons replaced by connective tissue. The pathogenesis of the disease has not been clarified yet. We have speculated that the increment of proliferation of bone marrow fibroblasts in IMF may be the consequence of the over-expression of some oncogenes, leading or contributing to the fibrosis via a cell amplification. Thus, we investigated the possible role of the c-myb and B-myb genes in IMF and control bone marrow fibroblasts in different culture conditions to evaluate proliferation parameters in the absence or presence of serum. Using the reverse transcriptase polymerase chain reaction technique, we demonstrated that the kinetics of induction was similar for both c-myb and B-myb during the proliferation of normal bone marrow fibroblasts. When compared to normal controls, cultured IMF fibroblasts showed more elevated values of c-myb and B-myb RNA; furthermore, after a 72 hours stimulation with serum, c-myb and B-myb messages remained relatively high in myelofibrotic fibroblasts. Finally, after serum starvation, c-myb and to a lesser extent B-myb RNA levels remained unusually high in IMF fibroblasts, while under the same experimental conditions c-myb and B-myb messages became virtually undetectable in normal bone marrow fibroblasts. To our knowledge this work represents the first description of an abnormal behavior of these genes in IMF fibroblasts.

Gemcitabine alone or combined with cisplatin in relapsed or refractory multiple myeloma.

Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas > or = 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, th e response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.

Time-Dependent Kinetics of Tretinoin in Chronic Myelogenous Leukaemia during Intermittent Dose Scheduling: 1 Week On/1 Week Off.

OBJECTIVE: This study investigated the pharmacokinetics of tretinoin during alternating cycles of 1 week of tretinoin treatment and 1 week drug-free in patients with Ph1+ chronic myelogenous leukaemia (CML) in the chronic phase. PATIENTS: Eighteen patients with CML were treated with tretinoin 80 mg/m(2)/day (in two divided doses) for 7 consecutive days every other week (one cycle = 1 week on/1 week off). RESULTS: Body systemic exposure to tretinoin as determined by the area under the plasma concentration-time curve (AUC) decreased significantly during the first week of drug administration, from (mean +/- SD) 678.3 +/- 498.1 to 258.7 +/- 272.4 microg/L.h. In about 40% of the patients the decline in plasma concentrations was >/=80%, while 17% of the population did not experience any decline. On day 7 of cycle 1, the mean apparent oral clearance (CL/F) was 2.6 times the corresponding value on day 1. After 1 week without tretinoin, the mean AUC on day 1 of cycle 2 was lower (down 15%) but not statistically different from the corresponding value observed on day 1 of cycle 1; 62% of patients showed an increase in the AUC, which was 40% higher than the corresponding value on day 7 of cycle 1. On day 1 of cycle 6, the AUC and CL/F of tretinoin during a dosage interval were not statistically different from those observed on day 1 of cycle 1 and cycle 2. On all occasions the peak plasma concentration (C(max)) was strongly correlated to the corresponding AUC. No significant change in the time to observed C(max) (t(max)) and in the elimination half-life (t((1/2))) was observed during the whole study. These results confirmed that the metabolism of tretinoin is rapidly up-regulated in CML patients, with significant declines in plasma drug exposure during the first week of drug administration. After tretinoin was discontinued, a return to the noninduced state followed a mean time-cycle similar to the induction. The strong decrease in the apparent oral drug clearance and the absence of significant variations in the drug half-life demonstrated that the presystemic extraction of tretinoin is the main cause of the marked decline in plasma drug exposure. CONCLUSION: The favourable pharmacokinetic profile of tretinoin obtained by an intermittent regimen, 1 week on/1 week off therapy (vs continuous administration), suggests that such a therapeutic schedule is the most appropriate for the assessment of clinical efficacy in those pathologies in which its use is suitable.

[Idiopathic myelofibrosis. Main pathogenetic, prognostic and therapeutic aspects]. / Mielofibrosi idiopatica. Principali aspetti patogenetici, prognostici e terapeutici.

Primary myelofibrosis is a complex disorder characterized by bone marrow fibrosis with no apparent cause. It is known in literature under a wide number of terms, reflecting the variety of clinical features and the different pathogenetic hypotheses. In most cases it is plain that marrow fibrosis is secondary to a clonal myeloproliferative disorder and, in particular, to the presence of abnormal megakaryocytes secreting (MKDGF/PDGF); but probably some other growth factors synthesized by megakaryocytes and contained in platelet alpha-granules are involved. The molecular event that determines the advantage of the clonal growth is, at present, unknown, and the pathogenetic importance of some chromosome anomalies is still under discussion. Over the last years, besides megakaryocyte dysplasia, several fibrogenetic mechanisms such as a bone marrow immune damage have been taken into consideration. Studies on prognostic factors regarding the main clinical, hematological and histological parameters have given conflicting results, because of low incidence of the disease, different criteria used for the diagnosis, and different terms of the clinic presentation of the pathology. Although a great deal of progress has been made in terms of pathogenetic mechanisms, a lot of questions must be still definitively settled, further in depth studies still have to go into many matters.

[Biologic aspects and clinical use of granulocyte growth factor]. / Aspetti biologici e impiego clinico del fattore di crescita granulocitario.

Granulocyte colony stimulating factors (G-CSF) has a wide spectrum of action: it stimulates proliferation and differentiation of granulocyte-macrophage progenitors, it promotes the chemotactic activity of monocytes and granulocytes and it develops the antibody-dependent cytotoxicity of neutrophils. In vivo G-CSF induces leucocytosis and it hastens the granulocyte recovery after chemio-radiotherapy. So it has been used in many pathologies: aplastic anaemia, AIDS in treatment with antiviral drugs, myelodysplastic syndromes, acute leukemias and solid tumors. If G-CSF is administered after chemotherapy, both in acute leukemias and in solid tumors, it reduces the duration of neutropenia and the number of febrile episodes so that it is possible to give the whole therapy at the planned dosage with no delay. However G-CSF does not modify the incidence of complete remissions and the overall survival. G-CSF allowed the increase of dose-intensity in chemoresistent neoplasms even if this therapy is always complicated by a heavy extrahaematological toxicity. Moreover G-CSF shortens the total duration of neutropenia after autologous or allogenic bone marrow and peripheral stem cell transplantation even if the appearance of the first neutrophil is not accelerated.

[Hodgkin's lymphoma and secondary leukemias]. / Linfoma di Hodgkin e leucemie secondarie.

The increase of survival in patients with Hodgkin's disease (HD) has made appear the problem of secondary neoplasms, included acute leukemias. The authors evaluate the incidence of acute leukemias in 205 HD with a follow-up more than 12 months (mean 92 months). With regard to these latter, 18 (8.7%) were treated with radiotherapy alone, 69 (33.6%) with chemotherapy alone and 118 (57.5%) with a combination of radiotherapy and chemotherapy. Chemotherapy consisted of 2-12 courses of MOPP alone or in combination with ABVD. The relative risk of acute leukemias is 96.7 (CI 95%: 44.2-183.6): nine cases against an expectancy of 0.093. The risk changes during five-years periods, but not significantly, and it not declines after ten years from the diagnosis. Only the alkylating chemotherapy seems to be important to favour the onset of acute leukemias. Among the patients who received a number of courses of MOPP less or equal than 6 (177), seven developed an acute leukemia (relative risk 85.3; CI 95%: 34.3-175.9); among those who received more than 6 (9), two developed an acute leukemia (relative risk 333.3; CI 95%: 40.3-1204.1). Neither the addition of radiotherapy nor the stage nor the splenectomy nor the histotype favour the onset of acute leukemia.

[Peripheral neuropathy associated with Castleman's lymphoma]. / Neuropatia periferica associata a linfoma di Castleman.

Castleman's lymphoma is a rare clinicopathological entity and is often difficult to classify nosographically. From the histopathological point of view two variants are recognized, one hyalino-vascular and one plasma cellular. Moreover Castleman's lymphoma may be multifocal or unifocal (located within the thorax in 70% of patients). The plasma cellular variant is often associated with systemic symptoms such as fever, sweating, organomegaly, polyneuropathy, and mono- or polyclonal gammopathy. We describe a rare case of unifocal, plasma cellular-type Castleman's lymphoma located in the mediastinum, asymptomatic at onset but later dominated by neurological symptoms (chronic isolated polyneuropathy whose clinical expression was predominantly motor). A brief review is presented of the main clinico-histological characteristics of Castleman's lymphoma together with some hypotheses about the pathogenesis of the associated neuropathy.

[Polyneuropathies associated with lymphoplasmacytic dyscrasias: the clinical and instrumental characteristics of a 38-patient case load]. / Polineuropatie associate a discrasie linfoplasmacellulari: caratteristiche cliniche e strumentali di una casistica di 38 pazienti.

A varying percentage from 40 to 60% of patients having lymphoplasmacytic dyscrasias with a monoclonal component shows a clinical or subclinical polyneuropathy. From a different viewpoint, a monoclonal gammopathy has been detected in 10% of patients effected by chronic idiopathic polyneuropathy. A case study of 38 patients with lymphoplasmacytic dyscrasia subjected to clinical, immunohematological and electrophysiological examination revealed a high prevalence of polyneuropathy (84%), mainly axonal (72%) and often subclinical. The neuropathy was evenly distributed between patients having malignant and benign lymphoplasmacytic dyscrasias. No statistically significant correlation was found between the presence of neuropathy and the main clinical and immunohematological data. This supports the concept that the pathogenesis of polyneuropathy associated with lymphoplasmacytic dyscrasias may be multifactorial. Nor can it be ruled out that the paraprotein may in fact be secondary to the polyneuropathy or sometimes a simple coincidence.

[The soluble IL-2 receptor in malignant hemopathies]. / Il recettore solubile dell'IL-2 nelle emopatie maligne.

The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.

Treatment of autoimmune thrombocytopenic purpura.

One hundred and two patients with newly diagnosed autoimmune thrombocytopenic purpura (ATP) were treated with prednisone (1.5-2 mg/kg/day for 4 weeks). A favourable response, lasting more then 12 months, was obtained in 22,5% of the cases. Different therapeutic strategies, such as immunosuppressive drugs, high dose immunoglobulins, splenectomy and others, were applied in unresponsive or relapsed patients. In our case study, splenectomy has proved the most satisfactory (87% of positive results) thus representing, in our opinion, the only effective therapy for resistant or relapsed case.