Biomedical subjects

K Delasalle

Publications and source records attributed to K Delasalle.

At least 19 recordsLinked to original sources

PubMed2005

Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma.

BACKGROUND: Magnetic resonance imaging (MRI) has been a useful technique for the assessment of patients with multiple myeloma (MM). We evaluated the prognostic significance of different MRI patterns in symptomatic patients with MM. PATIENTS AND METHODS: A total of 142 symptomatic MM patients underwent MRI before treatment. MRI patterns of involvement were correlated with known prognostic variables, including the International Staging System (ISS), response to treatment and survival. RESULTS: Focal marrow lesions were identified in 50% of patients, diffuse marrow replacement in 28%, a variegated pattern in 14% and normal pattern in 8%. When patients with the diffuse pattern were compared with patients with the other MRI patterns, they had features of more advanced disease such as higher ISS, anemia, hypercalcemia, elevated lactate dehydrogenase and extensive marrow plasmacytosis. Response rate was similar among patients with different MRI patterns. Median survival was 24 months for patients with the diffuse pattern, 51 months for those with the focal pattern, 52 months for those with the variegated pattern and 56 months for patients with the normal pattern (P = 0.001). The presence or absence of a diffuse MRI pattern separated patients with ISS stages I and II into two subgroups with significantly different survival times of 28 months and 61 months, respectively (P = 0.01). Furthermore, a diffuse MRI pattern predicted inferior outcome regardless of whether or not patients had received high-dose therapy with autologous stem cell transplantation. CONCLUSION: Diffuse marrow replacement on MRI adds to the evaluation of patients with multiple myeloma and their management.

Aged↗

PubMed2004

Clinical outcomes with intensive therapy for patients with primary resistant multiple myeloma.

Clinical outcomes were evaluated in 89 consecutive patients with multiple myeloma that had not responded to dexamethasone-based primary therapy, who received early intensive therapy supported by autologous stem cell transplantation. Results were compared with those of 45 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the response rate was 69% including 16% with CR. Survival of 14 patients with CR (median >7.0 years) was significantly longer than those of 47 patients with PR (median 4.5 years) or of 28 patients who remained NR (median 2.2 years). CR occurred in 43% of patients with serum myeloma protein <1.5 gm/dl, in contrast to 7% of those with higher values, a finding similar to that observed previously for patients consolidated in PR. No prognostic factor was associated with PR and, in view of the high frequencies of PR or CR, all patients with primary resistant myeloma should be considered for early intensive therapy. The limited improvement of lifespan and disease-free survival for those in PR indicated the need for further treatment to achieve CR, the major surrogate marker for long survival.

Adult↗

PubMed2003

Asymptomatic Waldenstrom's macroglobulinemia.

A study was undertaken to evaluate the frequency and natural history of disease in patients with asymptomatic Waldenstrom's macroglobulinemia (WM). Among 132 consecutive, newly diagnosed patients with monoclonal IgM, 82 (27%) had symptomatic WM indicated by anemia, lymphadenopathy, or splenomegaly. Thirty-one patients had similar clinical features but were asymptomatic and followed without therapy until disease progression. There were 19 patients with monoclonal gammopathy of undetermined significance of IgM type (MGUS). In comparison to overt WM, patients with asymptomatic WM had significantly higher hemoglobin (Hgb) level (median, 12.1 v 9.7 g/dL), lower serum beta(2)-microglobulin (B(2)M) level (median, 2.4 v 3.4 mg/L), and similar IgM peaks (median, 2.2 and 1.8 g/dL). The IgM component was 3.6 g/dL or less in all patients with asymptomatic disease. For asymptomatic WM, median time to disease progression was 6.9 years with rare morbidity. Prognostic factors for early progression were Hgb <11.5 g/dL, B(2)M >or= 3.0 mg/L, and IgM peak >3.0 g/dL. Combinations of these variables defined three risk groups for progression with markedly different median times to progression of >5 years, 2 years, and 0.5 year, respectively. Response rate and survival after institution of treatment were similar to those of patients treated promptly for overt disease. We conclude that, among patients with WM, 27% were asymptomatic with slow disease progression before the need for chemotherapy. Since disease outcomes after treatment were similar to those of patients treated at diagnosis, patients with asymptomatic disease should be identified and followed without treatment for as long as risks of complications remain low.

Anemia↗

PubMed2002

Consolidation therapy of multiple myeloma with thalidomide-dexamethasone after intensive chemotherapy.

BACKGROUND: After myeloablative therapy for multiple myeloma, progression-free survival is shorter for disease in partial remission rather than complete remission. In an attempt to induce more frequent complete remission, we assessed thalidomide-dexamethasone in patients with stable partial remission after intensive therapy. PATIENTS AND METHODS: Twenty-one patients with multiple myeloma were identified with disease in stable partial remission after prior intensive therapy. Thalidomide-dexamethasone was given within 15 months after intensive therapy provided myeloma protein production had been reduced by >75% to a constant level for at least 4 months. Thalidomide was begun at a dose of 100 mg each evening, with increments of 50 mg every 7 days to a maximum of 300 mg. Dexamethasone was given concurrently in a dose of 20 mg/m(2) each morning for 4 days on days 1-4, 9-12 and 17-20, with resumption on day 35. The combination was continued for at least 3 months and patients with marked reduction of myeloma were maintained on thalidomide alone until disease progression. RESULTS: Marked further reduction of myeloma by at least 90% occurred in 12 patients (57%), including four (19%) with disease converted to complete remission. Disease has progressed in six of 21 patients, whose median total remission was 22 months. Common side effects of constipation, fatigue, paresthesias and dry skin were mild, dose-related and reversible. CONCLUSIONS: The combination of thalidomide-dexamethasone reduced tumor mass markedly in 57% of patients with stable, residual disease after myeloablative therapy. Such an effect may produce longer disease-free survival and/or preserve tumor sensitivity to later retreatment with previously effective drugs.

Adult↗

PubMed2001

Impact of complete remission with intensive therapy in patients with responsive multiple myeloma.

Clinical outcomes were assessed in 68 consecutive patients with multiple myeloma of high or intermediate tumor mass that had responded to VAD or dexamethasone-based therapy and were consolidated with early intensive therapy and autologous stem cell transplantation. Results were compared with those of 50 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the rate of CR increased from 6 to 37%, with median survival prolonged by 10 months. Survival of 21 patients with disease converted from PR to CR (median 8.3 years) was significantly longer than that of similarly-treated patients who remained in PR (median 5.0 years). CR of myeloma represents the major surrogate marker of long survival and the primary goal of myeloablative treatment for patients in PR. Twelve of 18 patients with rapid reduction of myeloma protein (T(1/2) < 0.5 months), and myeloma protein reduction to <1.0 g/dl after primary therapy achieved CR (67%), identifying pretransplant features favorable to intensive therapy. Among 35 patients with slower reduction or higher residual myeloma protein, CR occurred in eight patients (23%) (P < 0.01), for whom other treatments should be considered. The kinetics of response to initial therapy should be considered in selecting patients more likely to achieve CR and consequent long survival after intensive treatment.

Actuarial Analysis↗

PubMed2000

Randomized trial of alpha-interferon or dexamethasone as maintenance treatment for multiple myeloma.

In order to assess the role of alpha-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with alpha-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone.

Adult↗

PubMed2000

Imaging of myeloma bone disease--implications for staging, prognosis and follow-up.

Among all imaging modalities, magnetic resonance imaging provides the most useful information about the accurate staging of solitary bone plasmacytoma, the prediction of progression of asymptomatic multiple myeloma and the prognosis of symptomatic multiple myeloma. Furthermore, magnetic resonance imaging contributes to the differential diagnosis of compression fractures in patients with myeloma and can be used for assessment of response to treatment.

Diagnosis, Differential↗

PubMed1999

Clinical course of solitary extramedullary plasmacytoma.

BACKGROUND AND PURPOSE: Solitary extramedullary plasmacytoma (EMP) represents a rare category of malignant disease on which there are limited data in regard to diagnosis, staging and natural history. This study attempted to clarify the clinical course of solitary extramedullary plasmacytoma after radiation or surgical therapy given with curative intent. MATERIALS AND METHODS: The diagnosis was based on a mass of clonal plasma cells separate from bone or bone marrow without evidence of occult disease elsewhere. Between 1963 and 1996, 22 previously untreated patients with an EMP were diagnosed. Disease presented in the head or neck in 86%, usually in the nasal cavity (NC) or maxillary sinus (MS), and in these areas local bone destruction was found in 10 of 11 patients. Among all patients, serum myeloma protein was present in three patients (14%) and Bence Jones protein alone was found in two patients (9%). Radiation therapy was the sole treatment for 18 of 22 patients, and the median radiotherapy dose was 50 Gy (range, 40-60 Gy); five of seven patients with an EMP of oral cavity (OC), oropharynx (OP), nasopharynx (NP), parotid or larynx also received elective neck irradiation. Two patients underwent surgery plus postoperative irradiation of a plasmacytoma of the sigmoid colon or pleura, and two patients had resection alone of a plasmacytoma of the colon or cervical lymph node. RESULTS: Local control was achieved in 21 of 22 patients (95%), and disease never recurred in regional nodes. Disappearance of myeloma protein occurred in three of five patients with an evaluable abnormality. Multiple myeloma developed in seven patients (32%), all within 5 years. The 5-year rate of freedom from progression to multiple myeloma was 56% and the median survival was 9.5 years. CONCLUSION: Radiation therapy achieved excellent locoregional control of EMP with an approximate cure fraction of 50%.

Adult↗

PubMed1998

Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy.

PURPOSE: To clarify the natural history of solitary plasmacytoma of bone (SBP) after radiation treatment. METHODS AND MATERIALS: Between 1965-1996, we identified 57 previously untreated patients with a SBP. A serum myeloma protein was present in 33 patients (58%) and Bence Jones proteinuria was present in an additional eight patients (14%). The median radiotherapy dose was 50 Gy (range, 30-70 Gy). Overall survival, cause-specific survival, and freedom from progression to multiple myeloma were calculated actuarially. RESULTS: Local control was achieved in 55 of 57 patients (96%). For those 29 patients (51%) who subsequently developed multiple myeloma, the median time to progression was 1.8 years. There was a direct correlation between persistence of abnormal protein following radiotherapy and the likelihood of developing multiple myeloma. Among 11 patients with disappearance of myeloma protein, only two developed multiple myeloma after 4 and 12 years, in contrast to progression in 57% of patients with a persistent protein peak and 63 % of those with nonsecretory disease (p = 0.02). Among 23 patients with thoracolumbar spine disease, 7 of 8 patients staged with plain radiographs alone developed multiple myeloma in comparison with 1 of 7 patients who also had magnetic resonance imaging (MRI) (p = 0.08). For all patients, the median survival from radiotherapy was 11.0 years. The median cause-specific survival of patients with disappearance of myeloma protein was significantly longer than that of the remaining patients (p = 0.004). CONCLUSION: Results supported the importance of precise staging that includes MRI of the spine for optimum patient selection and the application of definitive radiotherapy. Those patients with myeloma protein that disappears following radiotherapy represent a category with a high likelihood of cure.

Adult↗

PubMed1998

Prognostic value of cytogenetics in multiple myeloma.

Karyotypic studies of bone marrow were conducted in 79 previously untreated patients with multiple myeloma who received a standard programme of chemotherapy. An abnormal karyotype was observed in 46% of patients, virtually all showing multiple abnormalities consistent with a long period of preclinical clonal evolution. Patients with an abnormal pattern showed various aberrations with hyperdiploidy in 64%, pseudodiploidy in 5% and hypodiploidy in 31%. The number of chromosomes affected ranged from two to 19 (median 10), with at least one trisomy in 83%, one monosomy in 75%, and one translocation in 42% of patients. Lymphoma-like karyotypes were present in 17% of patients with an abnormality but were not associated with atypical clinical features, such as an extramedullary mass, leukaemia, or increased serum lactate dehydrogenase. Monosomy or deletion of chromosome 13 was present in 47% of patients with an abnormal pattern, who lived for a shorter duration (median 10 months) than patients with other abnormalities (median 34 months) or with diploidy (median 35 months). The cause of the short survival of patients with monosomy or deletion of chromosome 13 was not clear, but further studies on the relationship with specific oncogenes are indicated.

Bone Marrow Cells↗

PubMed1997

Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

PURPOSE: To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS: Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS: All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION: Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

Adult↗

PubMed1994

Early myeloablative therapy for multiple myeloma.

The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated within 1 year of initial therapy. Forty-five patients were consolidated during remission, and 27 patients were treated for primary refractory disease. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients who had responded previously, myeloablative therapy increased the rate of complete remission from 5% to 45% (P < .01) but did not prolong progression-free intervals or survival times. The same treatment controlled the myeloma in 70% of patients with primary resistant disease and prolonged the median survival from 37 to 83 months (P = .03). Intensive treatment for primary resistant myeloma administered later in the disease course resulted in significantly lower response rates and shorter progression-free intervals. Current myeloablative regimens supported by autologous stem cells appeared useful primarily in patients with primary resistant disease during the first year of therapy.

Adult↗

PubMed1994

Limited value of myeloablative therapy for late multiple myeloma.

The utility of myeloablative therapy supported by autologous bone marrow (BM) or blood progenitor cells was assessed in 49 patients with multiple myeloma who had received at least 1 year of prior chemotherapy. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients with disease in resistant relapse despite treatment with vincristine-doxorubicin by continuous infusion with pulse dexamethasone (VAD), a 61% response rate was associated with a median remission time of 5 months. After primary resistance for more than 1 year, 6 of 15 patients responded and the overall survival was similar to that of control patients. For patients with melphalan-resistant disease that responded to VAD, the remission time was similar to that of control patients. Current myeloablative treatments supported by autologous BM or blood stem cells were useful to very few patients with multiple myeloma after the first year of chemotherapy.

Adult↗

PubMed1994

Primary therapy of multiple myeloma with paclitaxel (taxol).

BACKGROUND: The treatment of multiple myeloma remains unsatisfactory and new active agents are needed. Paclitaxel is effective against a variety of solid tumors and we assessed the utility against multiple myeloma. PATIENTS AND METHODS: From March 1993 to May 1994, we treated 33 patients with newly diagnosed multiple myeloma with paclitaxel given intravenously at a dose of 125 mg/m2 over 24 hours (13 patients) or at a dose of 135 mg/m2 over 3 hours (20 patients). RESULTS: Five of 33 patients responded (15%; 95% CI: 5 to 32%) with an unmaintained remission of 3-11+ months. Severe but reversible neutropenia was the major dose limiting toxicity, but myalgias and alopecia were also common. CONCLUSION: Paclitaxel was slightly active against multiple myeloma. Whether higher doses or new analogues of this agent can produce superior results requires further study.

Adult↗

PubMed1994

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.

PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.

Adult↗

PubMed1994

Intensive sequential therapy for VAD-resistant multiple myeloma.

Few effective regimens are available for patients with advanced multiple myeloma resistant to alkylating agents and VAD. We treated 65 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 gm/m2) and etoposide (900 mg/m2) followed by GM-CSF at a daily dose of 0.125 mg/m2. Thirty-five percent of patients responded with a 6% mortality rate. After a median of 2 months, 16 patients received myeloablative treatment supported by autologous bone marrow or blood stem cells. Four of ten previously resistant patients responded so that the overall response rate was 42%. The median survival for all patients was 10 months and the median remission was 8 months. The median survival for patients with both low serum lactate dehydrogenase and B2 microglobulin, or for those who received myeloablative treatment, was projected at 18 months. Our combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This program allowed early blood stem cell collection in support of subsequent myeloablative therapy for selected patients.

Adult↗

PubMed1993

Treatment of Waldenstrom macroglobulinemia with 2-chlorodeoxyadenosine.

OBJECTIVE: To evaluate the activity of 2-chlorodeoxyadenosine (2CdA) in the treatment of patients with Waldenstrom macroglobulinemia. DESIGN: Uncontrolled phase II trial. SETTING: Tertiary, referral cancer center. PATIENTS: Twenty-nine consecutive, symptomatic patients with Waldenstrom macroglobulinemia, of whom 9 were previously untreated. INTERVENTION: 2-Chlorodeoxyadenosine was administered as a continuous intravenous infusion at a dose of 0.1 mg/kg body weight per day for 7 days. Only two courses of 2CdA were given and responding patients were then followed without further treatment. MEASUREMENTS AND MAIN RESULTS: A total of 17 (59%) patients responded, including all of those who were newly diagnosed and 40% of those who had failed previous therapies. Treatment was well tolerated except for one death in a patient who had presented with severe pancytopenia. With a median follow-up of 7 months, only one responding patient has relapsed. CONCLUSION: 2-Chlorodeoxyadenosine is a nucleoside analog that was effective in most patients with Waldenstrom macroglobulinemia and was associated with little toxicity.

Adult↗

PubMed1993

Fludarabine therapy in Waldenström's macroglobulinemia.

PURPOSE: To assess the response rate, remission duration, and survival of patients with Waldenström's macroglobulinemia treated with the adenine nucleoside analogue fludarabine. PATIENTS AND METHODS: Twenty-eight patients with Waldenström's macroglobulinemia, of whom only 2 were previously untreated, received fludarabine at a dose of 20 to 30 mg/m2 intravenously daily for 5 days (20 patients) or 30 mg/m2 intravenously daily for 3 days (8 patients). Treatment was continued until maximum response was achieved. Responding patients were followed with no further treatment until relapse. RESULTS: Ten patients responded (36%), including the 2 previously untreated patients and 8 of 26 patients (31%) who were resistant to prior therapies. Unmaintained remissions lasted for a median of 38 months. There were no fatalities associated with this treatment. Previously untreated patients and those with a primary resistant disease of relatively short duration were more likely to benefit from this treatment. CONCLUSION: Fludarabine is an effective salvage agent for the treatment of patients with resistant Waldenström's macroglobulinemia. Further investigations of fludarabine in untreated patients and in combination with other active agents are warranted.

Adult↗