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M Cavo

Publications and source records attributed to M Cavo.

At least 19 recordsLinked to original sources
PubMed1998

High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma.

The present clinical trial was undertaken to investigate the toxicity and antimyeloma activity of busulfan (BU) and cyclophosphamide (CY) at the maximum tolerated doses of, respectively, 16 mg/kg and 200 mg/kg (BU-CY 4) as conditioning therapy for allogeneic bone marrow transplantation (BMT) in 19 consecutive patients with multiple myeloma (MM). Twelve (63%) had failed to respond to prior chemotherapy, while the remaining 37% had chemosensitive disease. No life-threatening or fatal regimen-related complications were observed. The incidence of veno-occlusive disease of the liver was zero according to Jones' criteria and 21% according to McDonald's system. Transplant-related mortality was 37%. Using stringent criteria, the frequency of complete remission (CR) was 42% among all patients and 53% among those who could be evaluated. With a median follow-up of 21 months for all patients and 66 months for survivors, the actuarial probability of survival and event-free survival at 4 years from BMT was 26% (95% CI: 7-46) and 21% (95% CI: 3-39), respectively. A more favorable outcome of transplantation was observed in the subgroup of patients with chemosensitive disease who had a transplant-related mortality of 14%, an overall CR rate of 86% (95% CI: 49-97) and a 4-year projected probability of event-free survival of 57% (95% CI: 20-93). Four of these patients are currently alive in continuous CR after 54, 66, 80 and 94 months, respectively. It is concluded that BU-CY 4 as conditioning for allogeneic transplantation for MM is associated with acceptable morbidity and relatively low mortality. This regimen exerts substantial antimyeloma activity, resulting in a high CR rate and durable responses, especially in patients with chemosensitive disease. Long-lasting remission and probable cure is possible following allogeneic stem cell transplantation for MM.

Adult↗
PubMed1998

Allogeneic peripheral blood stem cell transplantation in patients with early-phase hematologic malignancy: a retrospective comparison of short-term outcome with bone marrow transplantation.

BACKGROUND AND OBJECTIVE: Transplantation of mobilized allogeneic peripheral blood stem cells (PBSC) has recently been reported by several groups. However, few patients receiving an allograft in the early stage of their disease have been described so far. DESIGN AND METHODS: Fifteen patients with early stage hematologic malignancies were transplanted with cryopreserved allogeneic PBSC from HLA-identical siblings. PBSC were collected after priming with 10 micrograms/kg/day of glycosylated granulocyte colony-stimulating factor (G-CSF, lenograstim). Outcomes were compared to a historical control group of 15 patients who received conventional bone marrow transplantation (BMT) from HLA-identical sibling donors. The two groups were matched for diagnosis, stage of disease, age, preparative regimen, graft-versus host (GVHD) prophylaxis, patients' and donors' gender and cytomegalovirus (CMV) serology. Diagnoses in both groups were: chronic myelogenous leukemia (CML) in first chronic phase (= 5), acute leukemia in first complete remission (CR) (= 5), non-Hodgkin's lymphoma in CR (= 1) and multiple myeloma (MM) with sensitive disease (= 4). All patients were given cyclosporin-A (CsA) and methotrexate (MTX) for GVHD prophylaxis. Preparative regimens varied according to diagnosis and included either busulfan/cyclophosphamide combination (BU/Cy) or total body irradiation/cyclophosphamide +/- melphalan (TBI/Cy +/- Mel). RESULTS: The patients in the PBSC group showed a more rapid hematopoietic reconstitution with a significant difference in the median times to 1 x 10(9) neutrophils/L (19 days vs. 26 days; p = 0.03) and to platelet transfusion independence (18 days versus 22 days; p = 0.02). This finding was associated with a significantly shorter hospitalization (28 days versus 33 days after transplantation; p = 0.01). In the PBSC series, grade II-IV acute GVHD occurred in 3 patients (20%) and grade III-IV in 1 patient (7%). In the BMT control group, grade II-IV aGVHD was reported in 2 cases (13%; p = NS) and 1 case had grade III-IV GVHD. Chronic GVHD developed in 7 patients (47%) (limited = 6; extensive = 1) undergoing PBSC transplantation and 5 patients (33%) (limited = 4; extensive = 1) in the BMT series (p = NS). No difference was found in the incidence of grade II-IV (according to the World Health Organization) mucositis, whereas PBSC recipients did have a significantly lower incidence of additional severe (grade III-IV) organ toxicity. After a median follow-up of 300 days (range 180-630), all PBSC patients are still alive with a median Karnofsky score of 100% (range 80%-100%). Thirteen patients are in CR and 2 myeloma patient are in good partial remission (PR). Also, in the BMT group the peritransplant mortality was absent; two MM patients died due to progressive disease at day +796 and +1,023, respectively; one leukemic patient died of chronic GVHD 407 days after transplantation and one additional leukemic individual relapsed 1,140 days after BMT. INTERPRETATION AND CONCLUSIONS: This retrospective comparison suggests that allogeneic PBSC transplantation performed in the early stage of the disease is safe and may be associated with a more rapid hematopoietic reconstitution than BMT, as well as lower transplant-related toxicity and earlier hospital discharge with apparently no increased risk of acute and chronic GVHD.

Adolescent↗
PubMed1997

Results of a fludarabine induction and alpha-interferon maintenance protocol in pretreated patients with chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma.

The activity of fludarabine monophosphate (FLU) and alpha-interferon (alpha-IFN) in low-grade non-Hodgkin's lymphoma (LG-NHL) and B-cell chronic lymphocytic leukemia (B-CLL) has been demonstrated in several clinical trials. In a study of 137 previously treated patients, of whom 77 had B-CLL and 60 with LG-NHL, we used FLU as salvage chemotherapy. Dosages of 25 mg/m2 were given in 30-min infusions for 5 consecutive d. Treatment was repeated every 28 d depending on the patient's clinical status for a maximum of 6 cycles. Entrance to the alpha-IFN maintenance portion of the study depended on patient response to initial FLU. All patients who had obtained a complete or partial response after the FLU therapy were randomized to receive alpha-IFN or no further therapy. The alpha-IFN dose was 3x10(6) units 3 times per wk until disease progression. At 4 yr with a median follow-up of 22 months the percentage of patients with persistent response ranged between 20% and 30% among all the responders. Thirty-five (45%) B-CLL patients achieved major responses (complete/partial response), as did 29 (48%) of those with LG-NHL. Among the 64 patients who achieved a good response to initial therapy and who have entered the second part of the trial, there has been a rate of prolongation of remission in favour of maintenance alpha-IFN (p=0.02). FLU therapy is an effective drug inducing remission in pretreated B-CLL and LH-NHL patients. However, as with other therapeutic modalities, remission is rarely maintained beyond 2 yr. So far, maintenance alpha-IFN has not been shown to produce significantly longer remission after treatment with FLU in LG-NHL, and there is no trend towards prolonged remission in B-CLL patients. The role of FLU needs to be further evaluated in the management of lymphoproliferative disorders by introducing it in combination with other drugs (alpha-IFN) in the induction phase and in maintenance treatment.

Adult↗
PubMed1997

Selection and transplantation of autologous hematopoietic CD34+ cells for patients with multiple myeloma.

Here we review our recent experience addressing the issue of positive selection and transplantation of hematopoietic CD34+ cells to reduce neoplastic contamination in peripheral blood (PB) autografts from patients with multiple myeloma (MM). We evaluated PB samples from 30 pretreated MM patients following the administration of high dose cyclophosphamide (Cy; 7g/m2 or 4g/m2) and granulocyte-colony stimulating factor (G-CSF), for collection of circulating stem cells (PBSC) to support hematopoietic reconstitution following myeloablative radio-chemotherapy. Twenty six patients showed adequate mobilization of CD34+ progenitor cells and were submitted to PBSC collection. Circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, cryopreserved, and used to reconstitute BM function after myeloablative therapy in 13 patients. The median purity of the enriched CD34+ cell population was 89.5% (range 51-94%) with a 75-fold increase compared to the pretreatment samples. The median overall recovery of CD34+ cells and CFU-GM was 58% (range 33-95%) and 45% (range 7-100%), respectively. Positive selection of CD34+ cells resulted in 2.5-3 log of plasma cells and CD19+ B-lineage cells depletion as determined by immunofluorescence studies, although DNA analysis of CDR III region of IgH gene demonstrated the persistence of minimal residual disease (MRD) in 5 out of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (TBI, 1000 cGy) and high dose Melphalan (140 mg/m2) or Melphalan (200 mg/m2) alone. They received a median of 5 x 10(6) CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis: the median time to 0.5 x 10(9) neutrophils, 20 and 50 x 10(9) platelets/L of PB was 10, 11 and 12 days, respectively. When we analyzed the immunological reconstitution of this group of patients, we observed a rapid and full recovery of total lymphocyte and NK cell count, although the absolute CD4+ cell count was lower than pretreatment level. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (=13) receiving unmanipulated PBSC following the same pretransplant conditioning regimen. The results of this trial demonstrate that positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3 log and provides a cell suspension capable of restoring a normal hematopoiesis after a TBI-containing conditioning regimen. Based on this pilot trial, we have recently started a clinical study involving a double autotransplant, conditioned with melphalan (200 mg/m2) followed by melphalan (140 mg/m2) and busulphan (14 mg/kg), supported by the reinfusion of highly purified CD34+ cells.

Antigens, CD34↗
PubMed1997

[Hepatitis A virus infection in children in Argentina: a pilot study].

UNLABELLED: The severity and/or the prognostic of infections with the hepatitis A virus (HAV) is related to the age at which the infection occurs. Since transmission of the virus occurs by the fecal-oral route, the prevalence and age-relate incidence of infection is determined by the adequacy of sanitation hygienic measures and the socio economic level of exposed populations. Thus, the disease is having an increasing impact in developing countries with improving sanitary standards whereas inhabitants of industrialized countries are particularly at risk while visiting under-developed countries. We have established a cooperative group for the serologic study of children range between six months to ten years old, without sintomatology of acute hepatitis. The patients live in Buenos Aires, San Justo, Trelew, Rosario and Tucumán cities. We studied 3699 children. The specific Ab-antiHAV IgG were measured by enzyme immunoassay with commercial available kits (Organon and-or Abbott). The variable of study were age, sex and water quality. RESULTS: 45.19% were of San Justo, 26.15% of Rosario, 13% of Buenos Aires, 8.37% of Trelew and 7.29% of Tucumán. We observed the highest of possibility percentage (%POS) in Tucumán (81.4%), followed by San Justo (57.8%), Rosario (46.5%), Trelew (41.99%) and Buenos Aires (29.4%). In all the cities the lowest %POS was found in children under three years old. Between three and six years old the results were variable and an increase in %POS was observed related to the growth. The global %POS was 51.56%. CONCLUSIONS: This study confirms Argentina as a high endemic country for HAV infection. A global vaccination program is the only strategy that has the potential to prevent recurrent epidemics of hepatitis A and its erradication.

Age Factors↗
PubMed1996

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗
PubMed1996

Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells.

One advantage of the use of peripheral blood stem cells (PBSCs) over autologous bone marrow would be a reduced risk of tumor cell contamination. However, the level of neoplastic cells in the PB of multiple myeloma (MM) patients after mobilization protocols is poorly investigated. In this study, we evaluated PB samples from 27 pretreated MM patients after the administration of high dose cyclophosphamide (7 g/m2 or 4 g/m2) and granulocyte-colony stimulating factor for the detection of myeloma cells as well as hematopoietic progenitors. Plasma cells containing intracytoplasmic lg were counted by microscope immunofluorescence after incubation with appropriate antisera directed against light- and heavy-chain lg. Moreover, flow cytometry studies were performed to determine the presence of malignant B-lineage elements by using monoclonal antibodies against the CD19 antigen and the monotypic light chain. Before initiation of PBSC mobilization, circulating plasma cells were detected in all MM patients in a percentage ranging from 0.1% to 1.8% of the mononuclear cell fraction (mean value, 0.7% +/- 0.4% SD). In these patients, a higher absolute number of PB neoplastic cells was detected after chemotherapy and granulocyte colony-stimulating factor. Kinetic analysis showed a pattern of tumor cell mobilization similar to that of normal hematopoietic progenitors with a maximum peak falling within the optimal time period for the collection of PBSCs. The absolute number of plasma cells showed a 10 to 50-fold increase as compared with the baseline value. Apheresis products contained 0.7% +/- 0.2% SD of myeloma cells (range, 0.2% to 2.7%). Twenty-three MM patients were submitted to PBSC collection. In 10 patients, circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, were cryopreserved, and used to reconstitute bone marrow function after myeloablative therapy. The median purity of the enriched CD34+ cell population was 89.5% (range, 51% to 94%), with a 75-fold increase as compared with the pretreatment samples. The median overall recovery of CD34+ cells and colony-forming unit-granulocyte-macrophage was 58% (range, 33% to 95%) and 45% (range, 7% to 100%), respectively. Positive selection of CD34+ cells resulted in 2.5- to 3-log depletion of plasma cells and CD19+ B-lineage cells as determined by immunofluorescence studies, although DNA analysis of CDR III region of IgH gene showed the persistence of minimal residual disease in 5 of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (1,000 cGy) and highdose melphalan (140 mg/m2). They received a median of 4 x 10(6) CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis; the median time to 0.5 x 10(9) neutrophils and to 20 and 50 x 10(9) platelets per liter of PB was 10, 11, and 12 days, respectively. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (n = 13) receiving unmanipulated PBSCs after the same pretransplant conditioning regimen. In summary, our data show the concomitant mobilization of tumor cells and hematopoietic progenitors in the PB of MM patients. Positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3-log and provides a cell suspension capable of restoring a normal hematopoiesis after a total body irradiation-containing conditioning regimen.

Adult↗
PubMed1996

Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of patients with multiple myeloma.

In this article, we review neoplastic contamination in the peripheral blood (PB) of patients with multiple myeloma (MM) upon stem cell mobilization. We first evaluated PB samples from pretreated MM patients following administration of high-dose cyclophosphamide (Cy, 7 g/m2 or 4 g/m2) and granulocyte colony-stimulating factor (G-CSF) for the presence of myeloma cells as well as hematopoietic progenitors. Plasma cells containing intracytoplasmic immunoglobulin (cIg) were counted by immunofluorescence microscopy after incubation with appropriate antisera against light and heavy chain Ig. Flow cytometry studies were performed to determine the presence of malignant B lineage elements, using monoclonal antibodies against the CD19 antigen and the monotypic light chain. Prior to PBSC mobilization, circulating plasma cells were detected in all MM patients at 0.1%-1.8% of the mononuclear cell (MNC) fraction (mean value 0.7 +/- 0.4% SD). In these patients, a higher absolute number of PB neoplastic cells was detected after administration of chemotherapy and G-CSF. Kinetic analysis showed a pattern of tumor cell mobilization similar to that of normal hematopoietic progenitors, with the peak coinciding with the optimal period for the collection of PBSC. The absolute number of plasma cells showed a 10-50-fold increase over the baseline value. Apheresis products contained 0.7 +/- 0.2% SD myeloma cells (range 0.2%-2.7%), which demonstrated the capacity of plasma cells to proliferate, differentiate, and mature in response to c-kit ligand (SCF), IL-3, IL-6, and a combination of IL-3 and IL-6. Subsequently, in an attempt to reduce tumor cell contamination prior to autologous transplantation, circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, cryopreserved, and used to reconstitute bone marrow (BM) function after myeloablative therapy in 13 patients. The median purity of the enriched CD34+ cell population was 89.5% (range 51%-94%), with a 75-fold enrichment compared with the pretreatment samples. The median overall recovery of CD34+ cells and CFU-GM was 58% (range 33%-95%) and 45% (range 7%-100%), respectively. Positive selection of CD34+ cells resulted in 2.5-3 log depletion of plasma cells and CD 19+ B lineage cells as determined by immunofluorescence studies, although DNA analysis of the CDR III region of the IgH gene demonstrated the persistence of minimal residual disease (MRD) in 5 of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (TBI, 1000 cGy) and high-dose melphalan (140 mg/m2) or melphalan (200 mg/m2) alone. They received a median of 5 x 10(6) CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis. The median time to 0.5 x 10(9) neutrophils, 20 x 10(9) and 50 x 10(9) platelets/L of PB was 10, 11, and 12 days, respectively. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (n = 13) receiving unmanipulated PBSC following the same pretransplant conditioning regimen. Our data demonstrate the concomitant mobilization of tumor cells and hematopoietic progenitors in the PB of MM patients. Positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3 log and provides a cell suspension capable of restoring normal hematopoiesis following a TBI-containing conditioning regimen.

Antigens, CD19↗
PubMed1995

An update of prognostic factors for allogeneic bone marrow transplantation in multiple myeloma using matched sibling donors. European Group for Blood and Marrow Transplantation.

Analysis of prognostic factors has been made in 369 allogeneic transplants for multiple myeloma reported to the registry of the European Group for Blood and Bone Marrow Transplantation (EBMT). Favorable prognostic factors for obtaining a complete remission (CR) were stage I at diagnosis (CR 77%), one line of treatment before conditioning (CR 52%), CR before conditioning (CR 60%), and Ig A or light chain myeloma (CR 43% and 42%). Factors that predicted significantly for favorable survival in a univariate analysis included having received only one line of treatment, female sex, stage I at diagnosis, stage I at conditioning and a beta 2-Microglobulin less than 4 mg/l. Favorable post-BMT factors consisted of obtaining a CR following BMT and not being in graft-versus-host disease stage III or IV. A multivariate analysis of pre-BMT factors showed that the sex of the patient and the number of lines of treatment pretransplant were independent prognostic factors. Allogeneic BMT is a promising treatment method for patients who have received only one line of treatment, particularly if they are of the female sex. BMT late in the course of the disease is usually unsuccessful.

Adult↗
PubMed1995

Allogeneic bone marrow transplantation for the treatment of multiple myeloma. An overview of published reports.

Allogeneic bone marrow transplantation (BMT) was first explored for the treatment of multiple myeloma (MM) in the mid 1980s. Since then, there has been a rapidly growing clinical demand for the use of this modality of treatment, so that the number of patients receiving worldwide transplants from HLA-identical siblings is actually estimated to be at least several hundreds. Although it is difficult to compare results between different centers because of differences in patient characteristics, selection criteria for transplantation and conditioning regimens, a certain number of conclusions have emerged from these experiences. There is evidence that allogeneic BMT performed in different phases of MM and with different conditioning regimens yields a high frequency of complete remissions (CR), in the range of 50% to 60%, and long-term survival and remission rates, both averaging approximately 20%. Although a toxic-related mortality rate of 40% has been consistently reported for many years, the outcome of patients in whom BMT was performed as consolidation of remission has recently improved. Prior responsiveness to conventional chemotherapy, also the presence of low tumor cell mass (both at diagnosis and before transplant) predicts for increased CR rate (up to 70% or more), as well as long-term survival and remission rates (both averaging approximately 50%). The continued relapse-free survival, up to and beyond ten years, reported for some of these patients provides strong evidence that allogeneic BMT has the potential ability to cure MM, probably as the result of an immunologic effect of the infused donor's marrow T lymphocytes against residual myeloma cells (graft-versus-myeloma).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1995

The role of haematopoietic stem cell-supported myeloablative therapy for the management of multiple myeloma.

Haematopoietic stem cell-supported myeloablative therapy appears to be a promising treatment modality for MM. It yields increased overall response and CR rates when compared with conventional chemotherapy, and seems to prolong the duration of survival. These conclusions, while encouraging, have mostly been drawn from uncontrolled studies carried out in select groups of patients and, obviously, need to be confirmed in controlled clinical trials. While the results of these studies are still awaited, the wider application of BMT should probably be encouraged. As in other malignancies, the best candidates appear to be those less heavily pre-treated, with chemosensitive disease, low tumour cell mass and other favourable prognostic features, for example low beta 2-microglobulin levels. Under these conditions, the chance of entering CR following BMT, be it autologous or allogeneic, is currently estimated to be of at least 50%, and the long-term probability of survival averages approximately 30%. However, while it appears that a plateau for progression-free survival cannot be ascertained following a single ABMT, reported observations of patients with continued disease-free survivals up to and beyond 10 years after allografting suggest that this latter procedure may be curative. It seems likely therefore that the higher mortality related to allogeneic BMT (which in recent years decreased from 50% to approximately 30% as the results of a better selection of patients and increasing experience in their management) may be offset by more durable control of the disease and cure in a certain proportion of patients. Recurrence of underlying malignant disease remains, however, a major problem and is the most common cause of treatment failure following BMT. For this reason, attempts to improve the impact of transplantation are warranted. Options currently under investigation include the development of more effective conditioning regimens, as applied in double auto-transplant or with targeted therapy using antibody-radionuclide conjugates, as well as post-transplant immunomodulation with either IFN-alpha, interleukin-2 or idiotype vaccines. In addition, many other problems regarding BMT for MM are still unresolved and could be properly addressed only in future clinical trials. The most important of these issues include the choice of the best conditioning regimen and the optimal source of haematopoietic stem cells, the nature of relapse after autografting, the need to purge or not to purge the autologous marrow, the existence of a 'graft-versus-myeloma' effect and its role in prolonging the duration of disease control and, finally, the likelihood of cure, especially for patients with molecularly-defined CR.

Antineoplastic Agents↗
PubMed1995

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different entities?

BACKGROUND: The objective of this study was to evaluate the similarities between solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EP). PATIENTS AND METHODS: The clinical features, treatment and survival of 54 patients with localized plasmacytoma (LP) 1990 were carefully reviewed. Follow-up was expected to continue until June 1993. RESULTS: Thirty-two patients were classified as having SPB and 22 EP. Most of the patients were males. particularly those in the SPB group. Their median age at diagnosis was 54 years and no significant difference between the two groups was observed. SPB occurred most frequently in the vertebral column (42%) and EP in the upper respiratory tract (73%). Fifteen patients with SPB and 2 with EP had paraproteinemia at diagnosis, multiple myeloma (MM) became evident in 75% of the patients with persistent paraprotein after therapy, and in only 22% of those in whom it disappeared. Four patients in the SPB group had immunoparesis, and 3 developed MM. Disease progression toward MM was significantly different (p=0.003) in the two groups, while overall survival differences were not significant (p=0.07) unless unrelated causes were excluded (p=0.02). Adjuvant chemotherapy did not seem to limit diffusion of the disease. CONCLUSIONS: Although EP and SPB are both localized forms of plasma cell dyscrasias, SPB seems to have a greater tendency to progression MM. It appears, however, that the apparent stronger propensity of SPB to progress is actually due to the great number of cases that at diagnosis conceal an occult MM.

Adult↗
PubMed1995

Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma.

PURPOSE: To analyze prognostic factors for allogeneic bone marrow transplantation (BMT) in multiple myeloma. PATIENTS AND METHODS: One hundred sixty-two reports of allogeneic matched sibling-donor transplants in multiple myeloma received by the European Group for Blood and Marrow Transplantation (EBMT) registry between 1983 and early 1993 were analyzed for prognostic factors. End points were complete remission, survival, and duration of complete remission. RESULTS: Following BMT, 44% of all patients and 60% of assessable patients entered complete remission. The overall actuarial survival rate was 32% at 4 years and 28% at 7 years. The overall relapse-free survival rate of 72 patients who were in complete remission after BMT was 34% at 6 years. Favorable pretransplant prognostic factors for survival were female sex (41% at 4 years), stage I disease at diagnosis (52% at 4 years), one line of previous treatment (42% at 4 years), and being in complete remission before conditioning (64% at 3 years). The subtype immunoglobulin A (IgA) myeloma and a low beta 2-microglobulin level (< 4 g/L) also tended to have a favorable prognostic impact. The most important post-transplant prognostic factor was to enter a complete remission. Grade III to IV graft-versus-host disease (GVHD) was associated with poor survival. CONCLUSION: Patients with a low tumor burden who respond to treatment before BMT and are transplanted after first-line therapy have the best prognosis following BMT.

Adult↗
PubMed1994

Expression and functional role of c-kit ligand (SCF) in human multiple myeloma cells.

In this study we investigated the proliferation of three well-documented MM lines and 10 bone marrow samples from myeloma patients in response to rh-SCF alone and combined with Interleukin-6 (IL-6), IL-3 and IL-3/GM-CSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (> 90%) by immunomagnetic depletion of T, myeloid, monocytoid and NK cells. The number of S-phase cells was evaluated after 3 and 7 d of liquid culture by the bromodeoxyuridine (BRDU) incorporation assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a clonogenic assay. All the experiments were performed in serum-free conditions. RPMI 8226 cell line was not stimulated by SCF which also did not augment the proliferative activity of IL-6, IL-3 and PIXY-321. Conversely, SCF addition resulted in 2.4-fold increase of the number of U266 colonies and in a higher number of U266 and MT3 cells in S-phase (24.5 +/- 2% SEM v 14.5 +/- 1% SEM and 32 +/- 3% SEM v 21 +/- 4% SEM, respectively; P < 0.05). The c-kit ligand also enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines. Anti-SCF polyclonal antibodies completely abrogated the proliferative response of MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the same cell line. Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was found, in a biologically active form, in the supernatant of the two cell lines by the MO7e proliferation assay. When tested on fresh myeloma samples, SCF increased the number of S-phase plasma cells (4.7 +/- 1.6% v 3.4 +/- 1.3% in control cultures: P = 0.02). Significant proliferation was also induced by IL-6 (7 +/- 2.3% of BRDU+ cells; P = 0.006), IL-3 (5.3 +/- 1.3%; P = 0.01) and PIXY-321 (5.4 +/- 1.6%; P = 0.02). The addition of SCF significantly enhanced the proliferation of myeloma cells responsive to IL-6. In summary, our results indicate that SCF is expressed in MM cells and stimulates the proliferation of neoplastic plasma cells.

Aged↗
PubMed1994

Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

Adult↗
PubMed1993

Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia.

In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.

Adult↗
PubMed1992

Allogeneic bone marrow transplantation in multiple myeloma.

The use of high-dose chemoradiotherapy with allogeneic hemopoietic stem cell support for the treatment of MM began about a decade ago. Because this procedure has been performed increasingly and because larger numbers of patients are being followed for longer periods of time, the proper role of allogeneic BMT in this setting is becoming clearer. Data available thus far indicate that such an approach results in a complete remission rate of at least 50% to 60%, and even higher if applied as consolidation treatment in the remission phase, a transplant-related mortality reported as 40% to 50% and a long-term survival plateau at around 40%. The 40% 5-year probability of relapse-free survival is considerably higher than that observed following autologous BMT and may result from an allogeneic graft-versus-tumor effect (graft versus myeloma) similar to the well-recognized graft-versus-leukemia effect. Although follow-up is still too short to clearly identify the likelihood of cure for MM allotransplant recipients, a certain number of them are currently long-term, disease-free survivors and--we hope--cured. These promising results and the incurability of MM with conventional chemotherapy should, therefore, encourage further application of allogeneic BMT to selected patients with unfavorable prognostic features. Continued efforts to reduce the morbidity and mortality related to the procedure, as well as to design effective pretransplant regimens with lower extramedullary toxicity and to identify those patients most likely to benefit from BMT, will improve the value of allogeneic BMT in MM.

Bone Marrow Transplantation↗