Characterization of a new HLA-DRB1 allele: DRB1*14:172.

DRB1*14:172 homologous to DRB1*14:01 has been found with a variation in 314 A > G.

Characterization of a new HLA allele: A*02:548.

HLA-A*02:548 differs from A*02:01:01:01 by one nucleotide at position 367T > C resulting in histidine at codon 99.

Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies.

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses.

High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors.

A total of 30 multiple myeloma patients (M=23, F=7; age 31-55 years, median 48) were allografted with peripheral blood stem cells (PBSC) from HLA-identical siblings. Time to transplantation was 3-107 months (median 8). Prior chemotherapy lines varied from 1 to 6 (median 1).

Dose-intensive melphalan with stem cell support (CM regimen) is effective and well tolerated in elderly myeloma patients.

Background And Objective: Multiple myeloma (MM) typically afflicts elderly patients. High-dose therapy has recently been shown to lead to a better outcome than standard treatment, mainly in younger patients. The extent to which older subjects can benefit from intensified approaches without excessive toxicity is examined in this study.

Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma.

In multiple myeloma (MM), allogeneic bone marrow transplantation may produce complete and durable responses, but is accompanied by significant transplant-related mortality (TRM). To assess feasibility and possible advantages offered by the use of allogeneic, growth factor-primed PBSC instead of marrow, we analyzed the data of 10 patients with MM (IgG = 6, IgA = 1, BJ = 2, non-secreting = 1; stage II = 1, stage III = 8, plasma-cell leukemia = 1) who received an allogeneic transplant with PBSC. Their age ranged between 35 and 53 years (median 45).

Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two.

Autoimmune hemolytic anemia during alpha interferon treatment in nine patients with hematological diseases.

BACKGROUND. A number of side effects have been observed in patients treated for hematological diseases with alpha-interferon (IFN). In several cases side effects consisted of immunological disorders.

High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion.

Mobilization of circulating progenitor cells in multiple myeloma during VCAD therapy with or without rhG-CSF.

Background: Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination.

Effect of alpha IFN on unaggressive immunoproliferative disorders.

Background: alpha-IFN is reported to be an effective treatment for a number of lymphoproliferative diseases. Little information is available at present on its effect in unaggressive immunoproliferative disorders.

Study Design And Results: In a prospective non randomized study, 57 patients with IgG or IgA MGUS, smouldering myeloma or stage I MM treated with alpha-IFN (3 MU 3 times a week for at least 6 months) were compared to 129 untreated similar patients.

A phase II trial on alpha-interferon (alpha IFN) effect in patients with monoclonal IgM gammopathy.

Waldenström's macroglobulinemia (WM) is an incurable disorder of B cells. Following occasional reports of response to alpha interferon (IFN) and in view of its effectiveness in hairy cell leukemia, we tested this agent in a relatively large group (n = 88) of patients who had an IgM monoclonal component (MC) greater than 10 g/l. Thirty eight patients had a MC > 30 g/l and were classified as Waldenström's macroglobulinemia (WM), while fifty had either WM in an early stage or an IgM monoclonal gammopathy of undeterminated significance (all of them operationally classified as IgM-MGUS).

High-dose therapy and autologous transplantation in amyloidosis-AL.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier.

Chromosomal abnormalities in Waldenström's macroglobulinemia.

We report the results of cytogenetic studies of direct bone marrow (BM) preparations and of short-term BM and peripheral blood (PB) cultures from 17 patients with Waldenström's macroglobulinemia. We noted clonal chromosome changes in 10 patients. Abnormalities affected chromosomes X, Y, 2, 4, 5, 15, 16, 18, 19, 20, 21, and 22; in particular, chromosomes 2, 4, and 5 were involved in structural changes: a homogeneously staining region [hsr(2)], a der(4)t(4;?)(q32;?), and a 5q+.

Assessment of blocking activity in patients with at least two consecutive spontaneous abortions.

The activity of the blocking factor (BF) was studied in 88 patients affected by recurrent abortion syndrome (RAS) by means of the determination of lymphocyte proliferation rate (LPR) in one-way mixed maternal-paternal lymphocyte cultures (MLC). Forty patients (45.5%) showed inadequate blocking activity (LPR greater than 80%).

Immunologic recurrent abortion: comparison between immunotherapies.

The Authors record the results in a group of patients with immunologic recurrent abortion (IRA) treated with two different immunoprophylaxis regimen. The first one is an active prophylaxis therapy with preparation and administration from donor mononucleates. According to their previous original experience, the Authors started giving high doses of IV-Ig (HD IV-Ig) in a second group of pregnant patients with the same diagnosis of immunologic recurrent abortion (IRA).

The use of three different therapeutic protocols according to the immunologic pathology present in three women with recurrent spontaneous abortion and fetal death for immunologic reasons: flucortolone and salicylates; high-dose intravenous gammaglobulins; subcutaneous heparin.

The authors report three cases of immunologic spontaneous abortions and fetal death. In the first patient there was lupus-like anticoagulant activity with a diagnosis of sub-clinical autoimmune disease; the second showed inadequate blocking factor activity, while the third subject presented excessive lymphocytotoxicity. In these cases three different therapeutic protocols were successfully used: flucortolone and salicylates, high-dose intravenous gammaglobulins and subcutaneous heparin.

New perspectives for the therapeutic management of recurrent immunological abortion.

Up to now the only effective therapy for recurrent abortion syndrome due to the absence of the so-called blocking-factor has been active immunotherapy with partner or third-party donor mononucleates. The Authors report their in vivo and in vitro experience with high-dose intravenous gammaglobulin (i IV Ig) in order to treat women with recurrent abortion syndrome. In the Authors opinion there are sufficient experimental reasons for continuing this research with IV Ig obtained from multiparous women plasma pools.

Immunological problems in the recurrent abortion syndrome.

The recurrent abortion syndrome has been considered a serious obstetrical problem, since it was not possible to diagnose the causes in over 40% of the cases. Great progress has now been made with the knowledge of the immunological mechanisms involved in the maintenance of pregnancy. The disorders of such immunological mechanisms, both due to auto- or alloimmune problems, are demonstrated in about 40% of the cases of recurrent abortions.

Artificial intelligence techniques for cancer treatment planning.

An artificial intelligence system, NEWCHEM, for the development of new oncology therapies is described. This system takes into account the most recent advances in molecular and cellular biology and in cell-drug interaction, and aims to guide experimentation in the design of new optimal protocols. Further work is being carried out, aimed to embody in the system all the basic knowledge of biology, physiopathology and pharmacology, to reason qualitatively from first principles so as to be able to suggest cancer therapies.