Biomedical subjects

A Fassas

Publications and source records attributed to A Fassas.

At least 37 records · Page 2Linked to original sources

PubMed2002

Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy.

Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.

Adult↗

PubMed2002

Transplantation as salvage therapy for high-risk patients with myeloma in relapse.

Patients with myeloma relapsing after tandem transplant have a poor survival and treatment options are limited. The role of additional salvage transplant procedures for these patients is unknown. To evaluate the benefit and identify prognostic factors, the outcome of 76 consecutive patients with recurrent myeloma after tandem transplant receiving salvage transplants (ST) was analyzed. Prior to ST, 23 patients (30%) had shown chemosensitive response to preceding salvage chemotherapy: two complete remissions (CR); eight near CRs (nCR: only immunofixation positive); 13 partial remissions (PR >or=75% reduction in M protein). Fifty received an autologous transplant, 22 a sibling-matched allogeneic transplant, and four a matched-unrelated allogeneic transplant. Overall response after ST was 59%: eight CRs (11%); 14 nCRs (18%); 23 PRs (30%). Overall survival (OS) at 2 years was 19%; 2 year event-free survival rate (EFS) 7%. On univariate analysis for survival, only pre-transplant chemosensitive relapse (P < 0.05), serum albumin >3 g/dl (P = 0.001), normal LDH (P = 0.04), and long interval between the second transplant and relapse/progression were significant beneficial factors. In a Cox proportional hazard model, chemosensitive relapse, and albumin >3 g/dl were significant for better OS: hazard ratio (HR) 1.4, 1.7, respectively, while normal LDH, and absence of CA13 were significant for better EFS: HR 1.8, 1.7, respectively. Patients with albumin >3 g/dl who had chemosensitive disease before ST (n = 16) had a median survival of 16 months, compared to 7 months (n = 34) and 2 months (n = 26) for patients with only one (n = 34) or no favorable prognostic factors (n = 28), respectively (P < 0.001). Their survival at 2 years post-ST was 43%, 17% and 11%, respectively. Our study suggests further transplantation should only be considered in the setting of a clinical trial in patients with favorable prognostic factors.

Adult↗

PubMed2002

Therapy-related myelodysplastic syndrome with monosomy 5 and 7 following successful therapy for acute promyelocytic leukemia with anthracyclines.

Myelodysplastic syndrome (MDS) in patients treated for acute promyelocytic leukemia (APL) is a rare event. We describe a patient with APL who developed MDS 40 months after entering complete remission (CR). Karyotypic analysis revealed monosomy 5 and 7, which are cytogenetic changes usually occurring after the use of alkylating agents. The patient had received only anthracyclines as potential leukemogenic drugs. A review of the literature on t-AML/MDS occurring after successful therapy for APL showed three similar cases. These observations suggest that anthracyclines may cause t-AML/MDS similar to that induced by alkylating agents.

Antibiotics, Antineoplastic↗

PubMed2002

Activated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications.

Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.

Activated Protein C Resistance↗

PubMed2002

Safety and early efficacy assessment of liposomal daunorubicin (DaunoXome) in adults with refractory or relapsed acute myeloblastic leukaemia: a phase I-II study.

We have conducted a phase I/II trial to determine the maximum tolerated dose, early safety and efficacy of single-agent liposomal daunorubicin in relapsed or refractory acute myeloid leukaemia (AML). Successive cohorts of six patients received escalated doses of 75, 100, 125 or 150 mg/m2 of DaunoXome for three consecutive days. Responding patients received a further consolidation cycle of DaunoXome at a dose identical to the one inducing complete or partial remission at the various dose levels. Twenty-eight patients with a median age of 50.5 years were enrolled. A maximum tolerated dose was determined at 150 mg/m2. Twelve patients received the second cycle. DaunoXome was well tolerated at all administered levels; dose-limiting toxicities included nausea and vomiting, mucositis and two episodes of cardiotoxicity resulting in the death of two patients. The overall response rate was 46% with a median duration of response of 180 d and a median duration of survival of 208 d. Ten patients demonstrated a complete response following cycle 1, and a further four entered partial response with the first cycle (marrow blasts between 5% and 10%). Of these, three attained complete response with the second cycle (total complete response 13/28). Our results indicate that DaunoXome at a dose of 150 mg/m2 displays acceptable toxicity in a 3-d regimen followed by a 3-d consolidation course at 100 mg/m2/d. At this dose schedule, interestingly high remission rates were achieved, justifying further evaluation of DaunoXome for the treatment of relapsed or refractory AML patients.

Adolescent↗

PubMed2001

High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions.

Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated with a high transplant-related mortality (TRM) in multiple myeloma (MM). Nonmyeloablative therapy can establish stable engraftment after allo-SCT and maintain the antitumor effect with less toxicity, which is important in heavily pretreated and elderly patients. We report on 16 poor-risk MM patients receiving allo-SCT from an HLA-matched (n = 14) or mismatched (n = 2) sibling following conditioning with melphalan 100 mg/m(2) (MEL-100). Ten patients had refractory relapse, 4 responsive relapse, and 2 patients were in near complete remission (nCR) with poor-prognosis disease. Patients had received 1 (n = 9) or 2 (n = 7) prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14 patients with no clinical evidence of graft versus host disease (GVHD) either to attain full donor chimerism (n = 4) or to eradicate residual disease (n = 10). Fifteen patients showed myeloid engraftment, and 12 patients were full donor chimeras at day +21. No TRM was observed during the first 100 days. Acute GVHD developed in 10 patients; 1 had fatal grade IV GVHD. Seven progressed to chronic GVHD, limited in 3 and extensive in 4 patients. At a median follow-up of 1 year, 5 patients achieved and sustained CR, 3 nCR, and 4 partial remission. Of 4 patients progressing after transplantation, 3 achieved a remission following further chemotherapy and DLI. Remarkable graft versus myeloma responses were seen in chemotherapy-refractory patients. Two patients died of progressive disease, and 3 died of GVHD complications without active disease. GVHD remains a major problem with this procedure.

Adult↗

PubMed2001

Results of high-dose treatment with autologous stem cell support in patients with multiple myeloma.

The introduction of high-dose treatment (HDT) with autologous hematopoietic stem cell support in patients with multiple myeloma (MM), although curative in only a minority of patients, has led to significantly longer event-free (EFS) and overall survival (OS) and likely improved quality of life compared with conventional chemotherapy. However, several issues remain unsettled. We review the current knowledge with respect to transplantation-related controversies, such as intensity of cytoreductive therapy (single v tandem transplants), optimal timing of the procedure, and potential benefit of graft purging and posttransplant consolidation chemotherapy. Special emphasis is placed on the safety and efficacy of transplant in elderly patients and in those with impaired renal function, who are usually excluded from the most effective therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Thalidomide in the management of multiple myeloma.

Thalidomide has recently been shown to have significant activity in refractory multiple myeloma (MM). A follow-up of the original phase II trial, expanded to 169 patients, shows 2-year survival of 60%; patients receiving > or =42 g over 3 months had a higher response rate and superior survival than those receiving lower doses. The addition of thalidomide to dexamethasone and chemotherapy for the management of post-transplant relapses results in higher response rates. The early results of the Total Therapy II trial for newly diagnosed MM patients show an unprecedented complete remission (CR) and near-CR rate of 69% after two melphalan-based transplants (whether or not receiving thalidomide). In addition, available clinical trial information involving at least 20 patients confirms that thalidomide is active in one third of patients in single-agent trials for refractory disease, with response rates increasing to 50% to 60% in combination with dexamethasone and to as high as 80% in combination with dexamethasone and chemotherapy. When applied as primary therapy in smoldering myeloma, one third of patients experienced 50% paraprotein reduction (PPR); in combination with dexamethasone pulsing, 70% to 80% of symptomatic patients responded. Thus, thalidomide is a major new tool in the treatment armamentarium of MM. The virtual lack of myelosuppression makes it an ideal agent for combination with cytotoxic chemotherapy. Newer, more potent, and less toxic derivatives of thalidomide are being evaluated.

Angiogenesis Inhibitors↗

PubMed2001

Collection of hematopoietic stem cells from patients with autoimmune diseases.

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 microg/kg/day) or cyclophosphamide (2 or 4 g/m2) with either G-CSF (5 or 10 microg/kg/day) or GM-CSF (5 microg/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). g-csf alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and g-csf (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted.

Adolescent↗

PubMed2001

Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy.

We report on three patients with multiple myeloma who developed drug-induced pneumonitis 1-2(1/2) months following maintenance (post autologous transplantation) chemotherapy with CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) and 6-20 months after exposure to carmustine (BCNU) 300 mg/m(2), used in combination with melphalan 140 mg/m(2), as pre-transplant conditioning regimen. All patients had either a proven (two) or suspected (one) fungal pneumonia and were treated with liposomal amphotericin B. Dyspnea, fever and cough were the prominent clinical symptoms, while air-space disease with ground glass appearance was seen radiographically. Histologic features typical for drug-induced lung injury were detected. All patients had a dramatic, clinical and radiographic response to a brief course of corticosteroids. Although CDEP-induced pneumonitis appears to be a rare complication, its early recognition and prompt treatment, as well as its possible association with preceding fungal infection may have important clinical implications.

Aged↗

PubMed2001

Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone.

Haematopoietic growth factors, especially granulocyte colony-stimulating factor (G-CSF), are frequently utilized alone for peripheral blood stem cell (PBSC) procurement to avoid the morbidity associated with high-dose chemotherapy (HDT). Moreover, the cytotoxic agents used may not be the most optimal therapy for the malignancy. It also makes scheduling of apheresis easier. Factors having an impact on PBSC procurement and engraftment after HDT were analysed in 117 multiple myeloma patients mobilized with G-CSF (10-16 microg/kg, median 12 microg/kg) alone using Cox regression analysis. A median of 6.2 x 10(6) CD34 cells/kg (range 0.6-34.1) were procured during leukapheresis and a median of 2.5 x 10(6) CD34 cells was infused after the first HDT (range 0.3-23.9). The only factor significantly affecting optimal PBSC procurement was duration of preceding conventional chemotherapy (P = 0.002). Granulocyte recovery was prompt in almost all patients, 75% of whom attained a granulocyte count of 0.5 x 10(9)/l by day 13 (median 11, range 7-19). However, platelet recovery to both 20 x 10(9)/l (median 12 d, range 8-50+) and 50 x 10(9)/l (median 20 d, range 7-205+) varied widely. On univariate analysis, factors influencing platelet recovery were the number of CD34 cells/kg infused, age, beta(2)-microglobulin levels, response to preceding therapy, bone marrow plasmacytosis and duration of prior therapy. Factors attaining significance on multivariate analysis included number of CD34 cells/kg infused (P = 0.007), beta(2)-microglobulin levels (P = 0.0001), most probably representing disease load, and age (P = 0.002). Patients with high tumour burden, i.e. beta(2)-microglobulin levels > 2.5 mg/l, probably benefit from chemotherapy for mobilization both in terms of cytoreduction and adequate stem cell mobilization resulting in accelerated engraftment.

Age Factors↗

PubMed2001

Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years.

The feasibility and efficacy of autologous stem cell transplantation (auto-SCT) in patients aged > or = 70 years was analysed. Newly diagnosed (n = 34) and refractory multiple myeloma (n = 36) patients were studied. The median age was 72 years (range: 70-82.6). CD34+ cells were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) (n = 35) or G-CSF alone (n = 35), yielding medians of 11.8 x 10(6) versus 8 x 10(6) cells/kg respectively (P = 0.007). Because of excessive mortality (16%) in the first 25 patients who received melphalan 200 mg/m2 (MEL-200), the dose was subsequently decreased to 140 mg/m2 (MEL-140). Median times to absolute neutrophil count (ANC) > 0.5 x 10(9)/l and to platelets > 20 x 10(9)/l were 11 and 13 d respectively. Thirty-one patients (44%) received tandem auto-SCT. Complete remission (CR) was 20% after the first SCT and 27% after tandem SCT. Median CR duration was 1.5 years and was significantly longer for patients with < or = 12 months of prior chemotherapy (2.6 versus 1.0 years, P = 0.0008). The 3-year event-free survival (EFS) and overall survival (OS) (+ standard error, SE) were projected at 20% + 9% and 31% + 10% respectively. Tandem SCTs positively affected EFS (4.0 versus 0.7 years; P = 0.003) and OS (4.0 versus 1.4 years; P = 0.02) compared with single auto-SCT. In conclusion, MEL-140 is less toxic and appears equally as efficacious as MEL-200 in elderly patients. The benefits of tandem SCT in this patient population need further evaluation in a randomized trial.

Aged↗

PubMed2001

Results of autologous stem cell transplant in multiple myeloma patients with renal failure.

Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.

Adult↗

PubMed2001

Cyclin D1 overexpression in multiple myeloma. A morphologic, immunohistochemical, and in situ hybridization study of 71 paraffin-embedded bone marrow biopsy specimens.

Cyclin D1 expression was evaluated by immunohistochemical analysis and biotin-labeled in situ hybridization (ISH) in a series of 71 decalcified, paraffin-embedded bone marrow biopsy specimens from patients with multiple myeloma (MM). Cyclin D1 messenger RNA (mRNA) overexpression was detected by ISH in 23 (32%) of 71 cases, whereas cyclin D1 protein was identified by immunohistochemical analysis in 17 (24%) of 71 specimens. All cases that were positive by immunohistochemical analysis also were positive by ISH. Statistically significant associations were found between cyclin D1 overexpression and grade of plasma cell differentiation and between cyclin D1 overexpression and extent of bone marrow infiltration. Our findings demonstrate the following: (1) ISH for cyclin D1 mRNA is a sensitive method for the evaluation of cyclin D1 overexpression in paraffin-embedded bone marrow biopsy specimens with MM. (2) ISH is more sensitive than immunohistochemical analysis in the assessment of cyclin D1 expression. (3) Cyclin D1 overexpression in MM is correlated positively with higher histologic grade and stage.

Antigens, CD20↗

PubMed2000

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.

High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (triangle up13) abnormalities and with beta-2-microglobulin </= 2.5 mg/L, C-reactive protein </= 4 mg/L, and pre-HDT standard chemotherapy </= 12 months. Of all 390 CR patients without triangle up13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with triangle up13 abnormalities. triangle up13 abnormalities, present in overall 16%, reduced 5-year event-free survival from 20% to 0% and overall survival from 44% to 16% (both P <.0001). CR and a second HDT cycle applied within 6 months both extended event-free and overall survival significantly, justifying further pursuit of HDT, especially toward curing non-triangle up13 MM. (Blood. 2000;95:4008-4010)

Adolescent↗

PubMed2000

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Blood Transfusion, Autologous↗

PubMed2000

Autologous stem cell transplantation in progressive multiple sclerosis--an interim analysis of efficacy.

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.

Adult↗

PubMed2000

Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone.

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483-487.

Antigens, CD34↗