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I Majolino,
P Corradini,
R Scimè,
M Falda,
A Bosi,
C Tarella,
M Musso,
A Olivieri,
M Boccadoro, R Marcenò,
A Santoro,
A Pileri
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ABSTRACT: 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). Four patients were in complete remission (CR), 11 in partial remission (PR), 13 were considered to be nonresponders, and two had progressive disease. Most were conditioned with busulfan-melphalan. PBSC were collected by apheresis after G-CSF or sequential GM-CSF and G-CSF. The patients were grafted with 4.4-24.1 x 10(6)/kg CD34+ (median 7.9) and 0.9-7.9 x 10(8)/kg CD3+ cells (median 2.3). GVHD prophylaxis was methotrexate-cyclosporine. Engraftment was complete and rapid. Grades II-IV acute GVHD (aGVHD) developed in 16 (53%), but was grade III-IV only in five (17%); chronic GVHD (cGVHD) developed in 17 out of the 24 evaluable patients (71%). A total of 18 patients (71%) attained CR after transplantation. TRM was 30% overall, 16% at 100 days. There was only one relapse. Overall survival and event-free survival at 73 months were 60% and 67%, respectively. PCR negativity for IgH-gene rearrangement occurred in all persistently CR patients studied. PBSC allograft can induce long remissions, because of profound suppression of the neoplastic clone that is probably linked to the antitumor effect of cGVHD.
Bone Marrow Transplantation 06/2003; 31(9):767-73. · 3.75 Impact Factor
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A Palumbo,
S Triolo,
L Baldini,
V Callea,
A Capaldi,
V De Stefano,
M Grasso,
M Liberati,
C Lotesoriere, R Marcenò,
F Marmont,
P Musto,
M T Petrucci,
M Spriano,
A Pileri,
M Boccadoro
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ABSTRACT: 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.
Between December 1994 and May 1997, 12 Italian Multiple Myeloma Study Group institutions entered 68 patients at diagnosis (median age 65) into an intensified chemotherapy regimen: cyclophosphamide (CY) 3 g/m(2) plus melphalan 60 mg/m(2) followed by peripheral blood progenitor cells (PBPC) and G-CSF (CM regimen). CY (day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis on day 10. Melphalan was infused on day 11. PBPC were kept unprocessed at 4 degrees C for 48 hours and reinfused on day 12. Three CM regimens were delivered at 6-month intervals.
Sufficient PBPC to support the first CM cycle were available (median CD34(+) harvest: 4.9x10(6)/kg), but dropped significantly after the second (median CD34(+) harvest: 2x10(6)/kg) and the third (median CD34(+) harvest: 0.9x10(6)/kg). The median durations of severe neutropenia (absolute neutrophil count < 500 microL) were 3, 4, and 3 days, and those of severe thrombocytopenia (platelets < 25,000/microL) were 2.5, 2, and 1 days, after the first, second and third courses, respectively. The frequency of extramedullary toxicities was low. Treatment-related mortality (TRM) was 3% after the first CM, only. Complete remission (CR) was 14% after the first, 16% after the second and 27% after the third CM. After a median follow-up of 34 months (range 19-49 months), median event-free survival was 35.6 months.
These results indicate that dose-intensity of melphalan can be increased by reinfusing PBPC with acceptable low toxicity. The combination of CY and melphalan followed by PBPC is an effective chemotherapy for elderly myeloma patients. Repeated melphalan infusion hampered subsequent CD34(+) harvests.
Haematologica 05/2000; 85(5):508-13. · 6.42 Impact Factor
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Haematologica 02/2000; 85(1):103-5. · 6.42 Impact Factor
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I Majolino,
P Corradini,
R Scimè,
A Santoro,
C Tarella,
A M Cavallaro,
A Palumbo,
A Indovina,
D Caracciolo,
M Boccadoro, R Marcenò,
A Pileri
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ABSTRACT: 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). All were HLA-identical to their sibling donors. Prior to allograft, six patients received standard-dose chemotherapy (DAV or CY-Dexa) and four a sequential intensified scheme with autologous PBSC support. At the time of transplantation, three patients were in CR, three in PR, three had refractory disease, one progressive disease. Patients were conditioned with busulfan-melphalan (n = 9) or busulfan-cyclophosphamide (n = 1), and were allografted with unmanipulated PBSC obtained by apheresis after treatment with G-CSF alone (n = 6) or GM-CSF followed by G-CSF (n = 4). All patients engrafted, with 0.5 x 10(9)/l PMN and 50 x 10(9)/l platelets on (median) day 13. Four patients had > or =grade II acute GVHD (grade II in 3, grade III in 1). Following allograft, CR was achieved in 71% patients. Eight are currently alive, with six in CR at a median of 18.5 months (range 7-28) from the transplant. Two patients died, 1 and 4 months from the allograft, respectively, and one is alive with progression. A PCR analysis of IgH rearrangement showed that residual disease was no more molecularly detectable in four out of seven evaluated patients following allograft. The results suggest that PBSC may improve the therapeutic efficacy of allogeneic transplant in MM, not only by a reduction of TRM but also by an improvement of rate and quality of response.
Bone Marrow Transplantation 09/1998; 22(5):449-55. · 3.75 Impact Factor
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I Majolino,
G Saglio,
R Scimè,
A Serra,
A M Cavallaro,
T Fiandaca,
S Vasta,
M Pampinella,
P Catania,
A Indovina, R Marcenò,
A Santoro
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ABSTRACT: 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. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.
Bone Marrow Transplantation 05/1996; 17(4):555-60. · 3.75 Impact Factor
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ABSTRACT: 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). All patients received IFN 3 MU/day for one month and then 3 times/week. Response to treatment was mainly based on MC reduction in two consecutive determinations (> 50%: major response; 25-50%: minor response). Of 36 evaluable WM patients, 12 had a major and 6 a minor response; of 41 evaluable IgM-MGUS patients, 2 had a major and 6 a minor response. In WM patients with a major response, MC reduction was associated with disappearance of hyperviscosity symptoms, raised Hb level and reduced bone marrow lymphoplasmacytosis. At the dose used, tolerance was excellent in the majority of patients; only 15% withdrew from the study due to side effects. Although single cases and very small series have already been reported, no large study collecting quantitative data on the effects of alpha IFN in WM has been published so far. Our results suggest that IFN treatment is not indicated for patients with a low monoclonal component, while it is of clinical benefit in about 50% of patients with IgM > 30 g/l.
Leukemia and Lymphoma 06/1994; 13(5-6):463-9. · 2.58 Impact Factor
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ABSTRACT: 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+. The other chromosomes were involved in numerical abnormalities, such as pseudodiploidy (a 46,X, -X, + 15 clone), loss of chromosome Y, and monosomy of chromosomes 16, 18, 19, 20, 21, and 22. Nonclonal chromosome rearrangements were also observed. The results are discussed in comparison with the few data reported in the literature, and the finding of an hsr in the long arm of chromosome 2 is emphasized; indeed, this is the first report of hsr in WM.
Cancer Genetics and Cytogenetics 08/1992; 61(2):147-51. · 1.39 Impact Factor
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ABSTRACT: Chromosome studies of five patients with myelofibrosis and myeloid metaplasia were carried out on bone marrow cells and/or on peripheral blood without PHA. Abnormal clones were found in three patients. Such clones were a minority, compared with the number of cells with normal karyotypes in all three patients. Chromosomes abnormalities consisted of 5q- (case 5), 13q- (case 2), and a small supernumerary acrocentric marker (case 3). One of our five patients, a woman aged 75 (case 1), showed a constitutional karyotype 46,XX,inv(5)( p15q11 ). The same chromosome rearrangement was present in 100% of the stimulated peripheral lymphocytes of this patient and in one of her sons with a normal phenotype. One patient (case 4) had a normal karyotype. These results are discussed and compared with data from the literature concerning myelofibrosis and other myeloproliferative diseases.
Cancer Genetics and Cytogenetics 08/1984; 12(3):209-15. · 1.39 Impact Factor
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ABSTRACT: 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. The Authors have studied a group of 56 patients with recurrent abortion syndrome in a complex diagnostic work-up involving: 1) The research of an autoimmune cause; 2) The research of the presence of the Blocking-factors by means of one-way mixed lymphocyte cultures; 3) The research of an altered antipaternal lymphocytotoxic activity or of an excessive HLA-sharing. According to the results of the investigations, several forms of therapeutic management have been used: 1) Steroids-aspirin-calcic heparin for Autoimmune cases. 2) Active immunotherapy for the cases due to the lack of blocking factors. 3) Calcic heparin for the altered antipaternal lymphocytotoxic activity. At the moment it is difficult to evaluate the results of pregnancy rate with this type of therapeutic management because of the too short follow-up.
Acta Europaea fertilitatis 20(4):199-202.
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ABSTRACT: 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%). Pearson's correlation did not reveal any link between patient age and LPR (m2 = 0.031), or between LPR and number of aborted pregnancy (m20.058). Fifteen of the 88 patients had had only two consecutive abortions, but Pearson's correlation did not result in any particular differences in the link between LPR and number of abortions in this group; we therefore felt perfectly justified in extending the study to these subjects.
Acta Europaea fertilitatis 22(3):177-9.
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Acta Europaea fertilitatis 22(5):267-74.
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ABSTRACT: 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 results of this not randomized study show better reproductive outcome in the group treated with use of HD IV-Ig.
Acta Europaea fertilitatis 22(3):171-5.
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Haematologica 68(2):287-8. · 6.42 Impact Factor
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ABSTRACT: 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. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.
Haematologica 78(1):68-71. · 6.42 Impact Factor
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ABSTRACT: 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. Autoimmune hemolytic anemia (AIHA) is the most typical example of an IFN-induced immune-mediated complication. CASE SERIES. In 10 years we observed 9 patients with various hematological disorders who developed AIHA during IFN treatment. The interval between the start of IFN treatment and the onset of acute hemolysis suggests a dual pattern of occurrence: (1) early onset (interval 1 to 21 days), seen in patients who had anti-RBC antibodies before IFN treatment; (2) late onset (interval 3-38 months), in patients with no history of anti-RBC antibodies at the start of treatment. Discontinuation of IFN, often associated with prednisone treatment, caused prompt hematological recovery in all cases; anti-erythrocyte antibodies persisted in the first group of patients and disappeared in the second. CONCLUSIONS. In rare cases IFN may cause AIHA. The immunological derangement caused by IFN seems to act at two different levels: enhanced destruction of antibody-coated RBCs and induction of autoreactive B-cells. As for the possibility of other preexisting immunological disorders, AIHA (even latent) is a contraindication to IFN treatment. Patients treated with IFN need accurate monitoring to guard against for the development of autoimmune disorders.
Haematologica 81(3):258-60. · 6.42 Impact Factor
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ABSTRACT: 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.
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. Four patients in the IFN group showed a monoclonal component reduction > 50% versus none in the control group, and 25% of patients suffered disease progression (MC increase > 50% and/or osteolytic lesions) in the IFN group as compared to 18% in the control group.
alpha-IFN administration at the dose used is ineffective for the majority of patients with slowly proliferating immunoproliferative disorders; only a small subgroup of them may benefit from such a treatment.
Haematologica 80(1):35-9. · 6.42 Impact Factor
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Haematologica 69(6):715-20. · 6.42 Impact Factor
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ABSTRACT: 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.
Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use.
Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly.
The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.
Haematologica 80(2):108-14. · 6.42 Impact Factor
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ABSTRACT: 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.
Acta Europaea fertilitatis 20(6):359-62.
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ABSTRACT: 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.
Acta Europaea fertilitatis 21(4):177-83.
