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Biomedical subjects

I Majolino

Publications and source records attributed to I Majolino.

At least 19 recordsLinked to original sources
PubMed2005

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.

Adolescent↗
PubMed2003

Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation.

Hepatitis B virus/hepatitis C virus (HBV/HCV) positive patients undergoing haemopoietic stem cell transplantation (HSCT) are at risk of hepatitis reactivation and fatal liver failure: we have conducted a retrospective study to assess the risk in 20 Italian transplant centres. A total of 90 patients infected with HBV (n=33) or HCV (n=57) receiving allogeneic (n=36) or autologous (n=54) haemotopoietic stem cell transplant (HSCT) between 1996 and 2000 were reviewed. The biochemical profiles and outcomes of infection-related liver disease were also analysed. The risk of death at 2 years was comparable when considering type of infection (3% for HBV vs 8% for HCV, P=0.6) or type of HSCT (7% for allogeneic vs 5% for autologous HHSCT, P=0.34). Hepatitis reactivation followed by resolution was more frequent in HCV+ than in HBV+ patients receiving an allograft (100% vs 16%, P=0.004). In HBV+ cases, risk of reactivation was comparable after autologous or allogeneic transplantation (66 vs 81%, P=0.3), but liver disease was more severe and occurred earlier in the autologous group. Our results indicate that HBV and HCV infection should not be taken as an absolute contraindication for HSCT and the risk of life-threatening liver complications are similar after allogeneic or autologous transplants.

Adult↗
PubMed2003

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). 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.

Adult↗
PubMed2003

Detection of minimal residual disease by real-time PCR can be used as a surrogate marker to evaluate the graft-versus-myeloma effect after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) is an effective and potentially curative treatment for some cases of multiple myeloma (MM). The curative efficacy of allo-SCT may be largely attributed to its immunological activity, the graft-versus-myeloma (GVM) effect. To evaluate the kinetics of residual myeloma cells, we analyzed the follow-up bone marrow samples of three MM patients by means of a real-time molecular assay. We identified a consistent correlation between onset of graft-versus-host disease and disease response. These data suggest that real-time molecular follow-up can be used to monitor the GVM effect and that it can be employed in the clinical setting to tailor post transplant immunomodulation.

Adult↗
PubMed2003

Intravascular B-cell lymphoma: report of two cases with different clinical presentation but rapid central nervous system involvement.

Intravascular lymphomatosis (IVL) is a rare large-cell lymphoproliferative disorder characterized by a widespread lymphoma proliferation within the lumen of medium and small vessels, frequently presenting with skin and/or central nervous system (CNS) manifestations. The tumor is of B-cell origin in most cases. Prognosis is poor with a reported median survival of 5-7 months. We describe here two cases of IVL. The first was that of a 55-year-old woman with a large B-cell lymphoma of the leg, successfully treated with conventional chemotherapy (CHT) followed by autologous peripheral stem cell transplantation. At 3 months from the autograft she relapsed with a picture of hemophagocytic syndrome (HPS) and CNS symptoms. She died before any specific treatment, and post-mortem examination revealed the intravascular proliferation of lymphoma B-cells in the brain and bone marrow. The second case was that of a 60-year-old male with CNS involvement at diagnosis. He responded poorly to CHOP-like CHT, and died 2 months after diagnosis and 6 months after onset of symptoms. Failure of CHT at least in some IVL patients may be related to a delay in the initiation of therapy due to non-specific neurological symptoms. Therefore, early diagnosis based upon aggressive attempts immediately followed by adequate therapy may prove beneficial to these patients. In the present report, we performed an extended medline-based review of the published series of patients with IVL.

Autopsy↗
PubMed2001

Cemp, a mitoxantrone containing combination, in the treatment of intermediate and high grade non-hodgkin's lymphoma: an effective and non toxic therapeutic alternative for adult and elderly patients.

Here we report the results of a randomised multicenter phase III clinical trial which assesses the therapeutic efficacy and tolerability of a chemotherapy protocol CEMP (cyclophosphamide, etoposide, mitoxantrone and prednisone) in adult and elderly patients with advanced intermediate and high-grade NHL. Between October 1991 and October 1995, 139 patients, aged 55 to 79 years, with diffuse intermediate and high-grade lymphoma, were enrolled. A considerable percentage of patients had clinically aggressive disease: 32.4% had systemic symptoms, 79% had stage III or IV disease, 33.8% had bone marrow involvement, 46% had splenic involvement and 42.5% had increased values of serum lactate dehydrogenate. Complete remission was achieved in 70 of the 139 patients (51.9%) and PR in 12 (16.6%) with an overall response of 68.5%. The overall response survival rate at 6 years was 39%, whereas DFS rate was 48.7% and PFS rate was 28.5%. At four years 49% of the patients were still in CR. Dividing the patients in two groups, under and over 65 years of age, we obtained the same results as far as overall response is concerned. No toxic deaths occurred, neither cardiac, renal nor liver complications happened. CEMP regimen is an effective and safe protocol with good results in elderly people, well comparable to those achieved in younger ones.

Actuarial Analysis↗
PubMed2000

Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor.

One hundred and one donors who had received filgrastim (rhG-CSF) for the purpose of donating either granulocytes or peripheral blood stem cells (PBSC) for their relatives more than 3 years ago were contacted. All donors had received daily rhG-CSF at a median dose of 16 microg/kg/day (range 3-16) for a median of 6 days (range 3-15 days). All collection procedures were completed and short-term side-effects of rhG-CSF were mild in the majority of the donors. At a median time interval of 43.13 months (range 35-73), the donors were contacted to assess whether adverse effects related to rhG-CSF administration had occurred. Prior to rhG-CSF two donors had cancer, one had a myocardial infarction, one was hepatitis C virus positive, one had a history of sinusitis, one had Graves' disease and two had arterial hypertension. None worsened with the rhG-CSF administration but the donor with a history of infarction had an episode of angina following apheresis, and the donor with Graves' disease had a stroke 15 months after rhG-CSF. Two pregnancies occurred after the rhG-CSF administration and one donor was 2-3 weeks pregnant during rhG-CSF treatment. Three pregnancies resulted in two normal births and one in a spontaneous abortion of a pregnancy which occurred more than 2 years following rhG-CSF. In the time following rhG-CSF administration two donors developed cancer (breast and prostate cancer) at a follow-up of 70 and 11 months, respectively. One donor developed lymphadenopathy 38 months after the rhG-CSF, which spontaneously resolved. Blood counts were obtained in 70 donors at a median follow up of 40.4 months (range 16.8-70.8). Hematocrit was 43% (median, range 36.8-48), white blood cells were 5.7 x 109/l (median, range 3-14), granulocytes 3.71 x 109/l (median, range 1. 47-10.36), lymphocytes 1.67 x 109/l (median, range 0.90-3.96), monocytes 0.46 x 109/l (median, range 0.07-0.87) and platelet counts were 193.0 x 109/l (median, range 175.0-240.0). This study indicates that short-term administration of rhG-CSF to normal donors for the purpose of mobilizing the PBSC or granulocytes appears safe and without any obvious adverse effects more than 3 years after the donation. Bone Marrow Transplantation (2000) 25, 85-89.

Adolescent↗
PubMed2000

Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma: an Italian Multicenter Study.

BACKGROUND AND OBJECTIVE: The outcome of patients with multiple myeloma (MM) has not changed markedly since the introduction of melphalan and prednisone. In recent years several studies have investigated the role of intensive therapy followed by infusion of autologous peripheral blood stem cells (PBSC) together with the administration of hematopoietic growth factors. In this study we evaluated the feasibility and efficacy of a PBSC transplantation program for patients with de novo MM in a multicenter setting. DESIGN AND METHODS: In a non-randomized controlled trial 52 patients with de novo MM from 6 Italian centers underwent a three phase treatment strategy including 3 cycles of VAD-like chemotherapy for initial debulking, followed by high-dose cyclophosphamide (HD-CY) and collection of PBSC, that were transplanted after a conditioning regimen with melphalan plus busulfan. Maintenance treatment was a conventional dose of interferon, given until relapse. Actuarial survival and response duration curves were plotted according to Kaplan and Meier's method; the groups were compared using the log rank test. Response rates were compared by the c(2) test; multivariate analysis was performed according to the stepwise regression model. RESULTS: Overall 39/52 (75%) of patients responded, with a complete remission (CR) rate of 31%. After a median follow-up of 55 months, median duration of event-free survival (EFS) and overall survival (OS) are 21 and 57 months, with 24% and 48% probabilities of being event-free and alive after 6 years, respectively. Among the group of 39 responders, CR was significantly associated with prolonged response and survival (2 deaths and 6 relapses/16 patients) as compared with PR (11 deaths and 15 relapses/23 patients), and remained the only significant variable also in a multivariate analysis. Myelosuppression did not protract beyond one week in transplanted patients; extra-hematologic toxicity was very low. INTERPRETATION AND CONCLUSIONS: This multicenter study confirms the feasibility of an aggressive approach to de novo MM patients. Additional confirmation is given of the increased rate of CR, and the significant prolonged survival observed in complete responders. In this experience the association melphalan plus busulfan was shown to be effective, at least as part of conditioning regimens, in the transplant strategy.

Adult↗
PubMed1999

Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells.

PURPOSE: To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells. MATERIALS AND METHODS: Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers. RESULTS: Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group. CONCLUSION: This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.

Adult↗
PubMed1999

Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Gruppo Italiano Trapianti di Midollo Osseo.

BACKGROUND AND OBJECTIVE: Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry. DESIGN AND METHODS: We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis. RESULTS: Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance. INTERPRETATION AND CONCLUSIONS: Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.

Adult↗
PubMed1998

Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation.

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors. Patients were stratified at randomization for age (</>/= 20 years), disease (acute leukemia, chronic myeloid leukemia [CML], nonneoplastic disease), disease status (early/advanced), and GvHD prophylaxis (cyclosporin/cyclosporin + methotrexate). Primary endpoints were response to treatment and evolution of aGvHD to grade III-IV. Secondary endpoints were cytomegalovirus (CMV) infections, transplant-related mortality (TRM), and relapse. The median interval between BMT and treatment was 12 days (6 to 43). Results in the two groups (2 v 10 mg/kg) were as follows: response of aGvHD 68% versus 71% (P = .9), evolution to aGvHD grade III-IV 17% versus 20% (P = . 6), CMV infections 55% versus 60% (P = .7), 3-year actuarial TRM 28% versus 32% (P = .7), relapse 17% versus 7% (P = .1). The actuarial survival at 3 years was 63% versus 62% (P = .9) with a median follow up of 580 and 778 days. On day 5 of therapy, 26 patients assigned to low-dose (2 mg/kg) 6MPred were switched to a higher dose of 6MPred because of no response or progression. Their actuarial TRM was 46%, which is significantly higher than TRM of patients who responded on 2 mg/kg and continued with tapering doses (TRM = 16%, P = .007). In conclusion, early treatment of acute GvHD with 6MPred 10 mg/kg/d does not improve the response rate as compared with 2 mg/kg/d, nor does it prevent evolution to aGvHD grade III-IV. CMV infections, TRM, and survival were also comparable. A group of patients at high risk of TRM can be identified after 5 days of treatment with 6MPred 2 mg/kg and could be eligible for alternative forms of therapy.

Actuarial Analysis↗
PubMed1998

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). 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.

Adult↗
PubMed1998

PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia.

We report the results of PBSC mobilization and immune selection in 17 patients with advanced chronic lymphocytic leukemia (CLL) enrolled in a multicenter Italian study of autologous transplantation with peripheral CD34+ selected cells. Mobilization was achieved by cyclophosphamide (CY) 4 g/m2 + G-CSF 5 microg/kg. CD34+ cells were positively selected by means of avidin-biotin immunoaffinity columns (Ceprate SC) or immunomagnetic beads (Isolex 300i) systems. Evaluation of minimal residual disease was performed by PCR analysis of the IgH gene rearrangment on the apheresis product before and after selection. Our results showed that after CY a median of 3.6 x 10(6)/kg (0.5-12.8) CD34+ cells were collected with a median of two aphereses in 14 out of 17 patients; three failed to mobilize a number of CD34+ cells adequate for subsequent manipulation. We found that in CR patients CD34+ cell yield per apheresis was significantly higher than in PR patients (P < 0.05). Sixteen selection procedures were performed in 13 patients. CD34+ cell recovery was 33.5% (10-85) with a median final yield of 1 x 10(6)/kg CD34+. Two patients underwent marrow collection due to the low number of CD34+ cells recovered. Final purity was 59% (range 22-94) and CD5/20+ cell depletion was 2.7 log (1.6-4.4). Our data showed a statistically higher CD34+ cell recovery and purity with the Isolex device compared to Ceprate (P < 0.01 and 0.01, respectively). All the evaluable samples remained PCR positive after selection. The main issues to be addressed in the future are the identification of patients who fail mobilization and the improvement of purging methods.

Adult↗
PubMed1998

Unrelated donor marrow transplantation for chronic myelogenous leukaemia.

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.

Adolescent↗
PubMed1998

VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

PURPOSE: The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B). RESULTS: There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed. CONCLUSION: In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.

Adolescent↗
PubMed1998

Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow.

BACKGROUND AND OBJECTIVE: Peripheral blood stem cells (PBSC) are being increasingly used as an alternative to conventional allogeneic bone marrow (BM) transplantation. This has prompted the Working Group on CD34-Positive Hematopoietic Cells to evaluate the current utilization of allogeneic PBSC in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of stem cell transplantation and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Review of the current literature shows that unmanipulated allogeneic PBSC give prompt and stable engraftment in HLA-identical sibling recipients. Despite the much higher number of T-cells infused, the incidence and severity of acute GVHD after PBSC transplant seems comparable to that observed with bone marrow (BM) cells. In comparison to the latter, PBSC probably ensure faster immunologic reconstitution in the early post-transplant period. Controversial results on the incidence and severity of acute-GVHD have been reported when CD34+ selection methods are used. Prospective randomized trials are underway to compare the results of PBSC and BM allogeneic transplantation. In mismatched family donor transplants, T-cell depleted PBSC successfully engraft immune-myeloablated recipients through a megacell-dose effect able to overcome the HLA barrier. Experience with PBSC in the context of unrelated donor transplants is currently anecdotal and prospective trials should be completed before that practice becomes routine. Finally, there is also limited evidence that, following induction chemotherapy, the addition of PBSC to donor lymphocyte infusion (DLI) for treatment of leukemia relapse after BMT may improve the safety and effectiveness of DLI itself. Concerning cord blood (CB) transplants, the most interesting aspects are the ease of CB collection and storage, the low risk of viral contamination and the low immune reactivity of CB cells. This last property has its clinical counterpart in an apparently reduced incidence and severity of acute GVHD both in sibling and unrelated CB transplants, probably making the level of donor/recipient HLA disparity acceptable a greater degree with respect to what is required for transplants from other sources.

Blood Cells↗
PubMed1998

bcr-abl rearrangement in adult T-lineage acute lymphoblastic leukemia.

The bcr-abl rearrangement in T-lineage ALL has been rarely described. In the last three years we studied all new patients with ALL at diagnosis by cytogenetic and molecular analysis. Three out of eleven T-lineage ALL patients presented the rearrangement and only one was Philadelphia positive.

Adolescent↗