Biomedical subjects

Raymond Alexanian

Publications and source records attributed to Raymond Alexanian.

17 recordsLinked to original sources

PubMed2006

Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib.

PURPOSE: To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma. PATIENTS AND METHODS: Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m2 intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13). RESULTS: Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m2 and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m2. Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade > or = 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy > or = grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%. CONCLUSION: Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.

Adult↗

PubMed2005

Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma.

BACKGROUND: Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma. METHODS: Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS: Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS: Retreatment with or continuation of bortezomib +/- dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.

Adult↗

PubMed2005

Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal function.

BACKGROUND: Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date. METHODS: Response rates, safety, and 20S proteasome activity were assessed in relation to baseline creatinine clearance (CrCl) among patients with recurrent and/or refractory myeloma (n = 256 patients) who were treated with bortezomib in 2 Phase II trials. Bortezomib was administered by intravenous bolus on Days 1, 4, 8, and 11 of a 21-day cycle at 2 doses, 1.0 mg/m2 (n = 28 patients) and 1.3 mg/m2 (n = 228 patients). RESULTS: Of 10 patients with CrCl < or = 30 mL/minute, 7 patients completed the protocol-specified 8 cycles of treatment; 4 patients received the 1.3 mg/m2 bortezomib dose, and 3 patients received the 1.0 mg/m2 bortezomib dose. Using the European Group for Blood and Marrow Transplantation criteria, responses were assigned by an independent committee to 3 of the 10 patients (2 partial responses and 1 minimal response), a response rate similar to that of the overall treated population. Patients with CrCl > 80 mL/minute (n = 105 patients), 51-80 mL/minute (n = 99 patients), and < or = 50 mL/minute (n = 52 patients) had similar rates of discontinuation and similar adverse event profiles. Renal function did not appear to affect the 1-hour postdose proteasome inhibition or its recovery. CONCLUSIONS: Clinical experience in a limited number of patients with impaired renal function suggests that bortezomib provides clinical benefit with manageable toxicities in this high-risk population.

Adult↗

PubMed2005

Thalidomide-dexamethasone as primary therapy for advanced multiple myeloma.

The value of thalidomide-dexamethasone was assessed in 26 consecutive, previously untreated patients with multiple myeloma of high tumor mass. All showed Hgb < 8.5 g/dL, serum calcium > 11.5 mg/dL, or both. The response rate was 73%, frequency of early death < 3 months was 5%, projected median survival was 30 months, and projected median remission time was 25 months. There were no occurrences of grade 3 or 4 neutropenia or thrombocytopenia, so that serious infection occurred in only 12% of patients. Thalidomide-dexamethasone was useful for these patients with advanced disease because of the high response rate and acceptable survival, with a low frequency of serious complications.

Adult↗

PubMed2005

How we treat Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma which produces monoclonal immunoglobulin M (IgM). Over the last decade, new treatment modalites have been developed for the management of this disorder. Our objective is to provide treatment recommendations for WM. A review of published reports was facilitated by a MEDLINE computer search and by a manual search of Index Medicus. Other sources included abstracts and conference proceedings. Most patients with WM who are diagnosed by chance without symptoms should not be treated. Initiation of treatment should not be based on level of serum monoclonal protein per se. The presence of cytopenia, significant adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy or cryoglobulinemia indicates the need for treatment. The main choices for primary treatment of symptomatic patients with WM include alkylating agents, the nucleoside analogs fludarabine or cladribine and the monoclonal antibody rituximab or combinations of these programs. There are no data from prospective randomized studies to recommend the use of one program over another. Nevertheless, the need for rapid disease control may favor the use of nucleoside analogs, whereas the presence of significant cytopenia may favor rituximab. High dose therapy with autologous stem cell transplantation may induce responses even in patients with resistance to all three class of agents. It may be prudent to avoid nucleoside analogs in patients who are candidates for high dose therapy. Despite the lack of randomized trials, a rational approach to the treatment of patients with WM is possible. Several factors, including the presence of cytopenias, need for rapid disease control, candidacy for autologous stem cell transplantation, age and co-morbid conditions, should be taken into consideration when choosing the most appropriate primary treatment.

Antibodies, Monoclonal↗

PubMed2004

Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma.

BACKGROUND: High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as part of the initial treatment regimen improves progression-free survival (PFS) and overall survival (OS) for patients with multiple myeloma. The optimal preparative regimen for patients with multiple myeloma has yet to be defined. In the current study, the authors compared the outcomes associated with high-dose melphalan (HDM) and a more intensive regimen of thiotepa, busulfan, and cyclophosphamide (TBC) in patients with multiple myeloma. METHODS: One hundred eighty-six patients with newly diagnosed multiple myeloma (median age, 51 years) received HDC with ASCT for consolidation of first remission (n = 108) or for treatment of primary refractory disease (n = 78). Seventy patients had a large tumor mass at the time of diagnosis. The preparative regimen consisted of TBC for 97 patients and HDM for 89 patients. Patients in the TBC group were younger and had more advanced disease stage at diagnosis and at the time of ASCT compared with patients in the HDM group. RESULTS: The response rates (complete response [CR] and partial response [PR]) were similar in the TBC group (overall response rate, 66%; CR rate, 17%; PR rate, 49%) and the HDM group (overall response rate, 69%; CR rate, 28%; PR rate, 41%). PFS and OS were similar in both groups. A proportional hazards regression model revealed that Durie-Salmon disease stage at diagnosis and having received three or more previous treatment regimens were the only factors that predicted PFS; the type of preparative regimen did not influence outcome. CONCLUSIONS: The results of the current study indicate that the use of a more intensive regimen did not improve results compared with HDM in patients with multiple myeloma. HDM should continue to be considered the standard preparative regimen for patients with myeloma.

Adult↗

PubMed2004

High-dose topotecan, melphalan and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of multiple myeloma.

The goal of this trial was to assess the toxicity and potential efficacy of high-dose topotecan, melphalan and cyclophosphamide as a preparative regimen for patients with multiple myeloma undergoing autologous stem cell transplantation. Eighteen patients were treated, 8 for first remission consolidation, 4 with relapse sensitive disease, 3 primary refractory and 3 relapsed refractory. The median age was 56 (38 - 65) and the median number of prior regimens was 3 (1 - 8). Patients received cyclophosphamide 1 g/m2/d on days -6, -5, -4; melphalan 70 mg/m2 on days -3, -2 and topotecan 3.0 to 3.5 mg/m2/d on days -6 to -2. Peripheral blood stem cells were infused on day 0. Toxicity (Bearman Toxicity Criteria) was mostly limited to grade 1 - 2 mucositis and grade 1 diarrhea. There were no transplant-related deaths. The overall response rate at 3 months post transplantation was 89% with 17% CR, 2 of those in refractory patients. The overall response rate in refractory patients was 67%. With a median follow up of 12.3 months, 89% of patients are alive. The TMC regimen is well tolerated and produces high response rates. Further evaluation of TMC to fully assess response and survival is ongoing.

Adult↗

PubMed2004

Treatment of Waldenstrom's macroglobulinemia with rituximab: prognostic factors for response and progression.

Recent data have suggested that rituximab is an active agent for the treatment of Waldenstrom's macroglobulinemia (WM). However, the patients that are more likely to benefit have not been clearly defined. In order to address this question we evaluated 52 patients who were treated with single-agent rituximab in the context of prospective studies. Several clinical and laboratory variables were assessed for their correlation with response and time to progression. Twenty-three (44%) patients achieved a partial response after treatment with rituximab. Previously untreated and pretreated patients had the same probability for response. Higher response rates were noted in patients with serum monoclonal protein < 40 g/l, with serum albumin > or = 35 g/l and with kappa light chain. The median time to progression for all patients was 13.8 months. A multivariate analysis indicated that elevated serum monoclonal protein levels and low serum albumin were the dominant variables associated with shorter progression. Presence of two, one or none of these adverse prognostic factors was associated with time to progression of 3.6 months, 11 months and more than 40 months, respectively. We conclude that rituximab is an effective treatment modality for patients with WM. Patients with both low levels of monoclonal protein and normal albumin are the best candidates for treatment with standard dose rituximab.

Aged↗

PubMed2003

Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis.

Chemoresistance is a major problem in the treatment of patients with multiple myeloma (MM). Because of the central role of the nuclear transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) in chemoresistance, cell survival, and proliferation, we investigated whether MM cells derived from patients express activated NF-kappaB and STAT3 and if their suppression induces apoptosis. We assayed CD138+ cells from the bone marrow of 22 MM patients and checked for the activated forms of NF-kappaB and STAT3 by immunocytochemistry. We found that MM cells from all the patients expressed the activated forms of NF-kappaB and STAT3 but to a variable degree (NF-kappaB: low, 3 of 22; moderate, 5 of 22; or high, 14 of 22; STAT3: none, 1 of 22; low, 3 of 22; moderate, 5 of 22; or high, 14 of 22). Constitutive activation of NF-kappaB was in some cases also independently confirmed by electrophoretic mobility gel shift assay. In contrast to MM patients, activated forms of NF-kappaB and STAT3 were absent in cells from healthy individuals. Suppression of NF-kappaB and STAT3 activation in MM cells by ex vivo treatment with curcumin (diferuloylmethane) resulted in a decrease in adhesion to bone marrow stromal cells, cytokine secretion, and in the viability of cells. When compared with curcumin, dexamethasone was less effective in suppression of NF-kappaB activation and induction of apoptosis in myeloma cells. Overall, our results indicate that fresh cells from MM patients express constitutively active NF-kappaB and STAT3, and suppression of these transcription factors inhibits the survival of the cells.

Adult↗

PubMed2003

A phase 2 study of bortezomib in relapsed, refractory myeloma.

BACKGROUND: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.

Adult↗

PubMed2003

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials.

Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation.

Adult↗

PubMed2003

Thalidomide alone or with dexamethasone for previously untreated multiple myeloma.

PURPOSE: To evaluate the activity of thalidomide in patients with asymptomatic multiple myeloma and of thalidomide-dexamethasone in patients with previously untreated symptomatic myeloma. PATIENTS AND METHODS: Twenty-eight patients with previously untreated asymptomatic myeloma were treated with thalidomide 100 to 200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at weekly intervals, as tolerated to a maximum of 600 mg PO qhs. Forty consecutive previously untreated patients with symptomatic myeloma were also treated as above (maximum dose 400 mg) and received dexamethasone 20 mg/m(2) for 4 days beginning on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were begun on day 30. Both groups of patients were treated for at least 3 months. RESULTS: The response rate was 36% for patients treated with thalidomide alone and 72% for patients treated with thalidomide-dexamethasone, the latter including complete remission in 16% of patients. The median time to remission was 4.2 months with thalidomide alone and 0.7 months with thalidomide-dexamethasone. Grade 3 toxicity included infections (nine patients) and thrombotic/embolic events (seven patients). Five deaths have occurred as a result of multiple myeloma (two patients), infection (one patient), unknown cause (one patient), and a possible thromboembolic event (one patient). CONCLUSION: Thalidomide alone was effective in patients with newly diagnosed myeloma. The combination with dexamethasone induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. These observations support further studies of this promising combination for patients with newly diagnosed multiple myeloma.

Angiogenesis Inhibitors↗

PubMed2003

Thalidomide and dexamethasone for resistant multiple myeloma.

Between November 1998 and April 2000, the combination of thalidomide and dexamethasone was evaluated in 47 consecutive patients with multiple myeloma that was resistant to prior high-dose dexamethasone-based therapies. Remission was observed in 22 patients (47%), including six patients with complete remission. Side-effects were frequent, mild and usually reversible, but deep vein thrombosis occurred in 8% of patients. Survival and remission times were longer among patients treated for previous resistant disease rather than for resistant relapse. This experience supports the use of thalidomide-dexamethasone in myeloma patients with resistant disease and justifies further trials in newly diagnosed patients.

Adult↗

PubMed2003

Thalidomide with or without dexamethasone for refractory or relapsing multiple myeloma.

Both thalidomide and intermittent high-dose dexamethasone are agents with established activity against multiple myeloma. We summarized our experience with thalidomide alone, and then in combination with dexamethasone, for groups of patients with myeloma resistant or relapsing despite standard treatments. Criteria of response were based on greater than 50% reduction of serum myeloma protein and/or greater than 75% reduction of Bence Jones protein for patients treated with thalidomide alone and greater than 75% reduction of serum myeloma protein and/or greater than 90% reduction of Bence Jones protein for those who received thalidomide with dexamethasone. Among patients with resistant or relapsing disease treated with a combination of thalidomide and dexamethasone, 47% of patients achieved remission with significant prolongation of survival for responsive patients. Among patients in stable partial remission after intensive therapy who received the same program, myeloma protein was reduced further by greater than 90% in 52% of patients who had not received prior thalidomide/dexamethasone. Side effects were frequent, mild and reversible, and often preventable. Our program of thalidomide/dexamethasone was a safe and effective combination for patients with resistant or relapsing disease, or as consolidation of partial remission after intensive therapy.

Adjuvants, Immunologic↗

PubMed2003

Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia.

This presentation represents consensus recommendations on prognostic markers and criteria to initiate therapy in patients with Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the Second International Workshop held in Athens, Greece during September 2002. The panel recommended that initiation of therapy should not be based on the IgM level per se since this may not correlate with the clinical manifestations of WM. The consensus panel agreed that initiation of therapy was appropriate for patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, or weight loss. The presence of progressive, symptomatic lymphadenopathy or splenomegaly provide additional reasons to begin therapy. The presence of anemia with a hemoglobin value of <or= 10 g/dL or a platelet count < 100 x 10(9)/L due to marrow infiltration also justifies treatment. Certain complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, renal insufficiency, or symptomatic cryoglobulinemia may also be indications for therapy. Recommendations for follow-up of watch-and-wait patients are that those with monoclonal gammopathy of undetermined significance (MGUS) should have serum protein electrophoresis repeated each year. Patients with asymptomatic (smoldering) macroglobulinemia should be evaluated every 6 months. Regarding prognostic markers, hemoglobin and beta(2)-microglobulin levels at diagnosis are important prognostic markers in WM: they influence the timing of treatment and survival. Age is a consistently important prognostic factor for survival. However, the panel felt that current data are inadequate to support the use of any prognostic marker to select the timing and type of therapy, and called for studies on the application of prognostic markers in WM.

Age Factors↗

PubMed2003

2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom's macroglobulinemia.

Treatment for Waldenstrom's macroglobulinemia (WM) has usually been reserved for symptomatic patients and has included alkylating agent-steroid combinations and, more recently, nucleoside analogues. We now describe our experience with 2-chlorodeoxyadenosine (2-CdA) alone and in combination at our center. We treated 90 consecutive, previously untreated patients with symptomatic WM using either 2-CdA alone or in combination with other agents including prednisone (pred), cyclophosphamide (Cy), and rituximab (Rit) as follows: January 1991 to December 1992- 2-CdA 0.1 mg/kg by continuous infusion (CI) over 24 hours for days (16 patients); December 1992 to December 1995-2-CdA 0.1 mg/kg CI over 24 hours for 7 days plus pred 60 mg/m(2) orally daily for 7 days (20 patients); July 1996 to March 1998-2-CdA 1.5 mg/m(2) by subcutaneous injection (SC) every 8 hours for 7 days plus Cy 40 mg/m(2) orally twice daily for 7 days (37 patients); August 1999 to December 2001-2-CdA 1.5 mg/m(2) SC every 8 hours for 7 days plus Cy 40 mg/m(2) orally twice daily for 7 days plus Rit 375 mg/m(2) by intravenous infusion (IV) weekly for 4 weeks (17 patients). For nearly all patients, a second course was repeated after at least 6 weeks. Responding patients were monitored without further treatment until relapse. Overall response (complete [CR] + partial response [PR]) was 94% for 2-CdA alone, 60% for 2-CdA/pred, 84% for 2-CdA/Cy, and 94% for 2-CdA/Cy/Rit. Median overall survival is 73 months for 2-CdA, 41 months for 2-CdA/pred, and has not been reached for 2-CdA/Cy or 2-CdA/Cy/Rit. Cause-specific survival for 2-CdA/pred is 78 months and has not been reached for all other programs. The only poor prognostic factor for cause-specific survival was hemoglobin < 9 g/dL. 2-CdA regimens provide excellent response rates and improve cause-specific survival, with minimal treatment and little toxicity. These observations support the potential role of 2-CdA regimens as the treatment of choice for previously untreated WM.

Aged↗

PubMed2002

Persistence of myeloma protein for more than one year after radiotherapy is an adverse prognostic factor in solitary plasmacytoma of bone.

BACKGROUND: Prognostic factors for solitary plasmacytoma of bone (SPB), whether measured before or after radiotherapy (RT), have not been established. The authors analyzed multiple factors for myeloma-free survival (MFS) and cause-specific survival (CSS) in SPB patients treated with RT alone. METHODS: Between 1965 and 2000, 60 patients with carefully staged SPB were treated with RT alone at the M. D. Anderson Cancer Center. Patient ages ranged from 29-77 years (median, 54 years), and 75% of patients had a myeloma (M) protein in the blood and/or urine. No patients showed other lesions on skeletal survey or, in recent years, magnetic resonance imaging (MRI) of the spine; marrow aspirate was normal in all patients. Radiotherapy to the solitary lesion was given to a total dose of 30-70 Gy (median, 46 Gy). The authors analyzed the impact of multiple factors on MFS and CSS, including resolution v. persistence of M protein after RT, secretory v. nonsecretory disease at diagnosis, presence v. absence of an associated soft tissue mass on computed tomography or MRI scan, magnitude of serum M protein elevation at diagnosis, age, spinal v. nonspinal location, Karnofsky performance status, total RT dose, and tumor size. RESULTS: Median follow-up was 7.8 years (range, 1.0-25.5 years). On multivariate analysis, persistence of M protein more than one year after RT was the only independent adverse prognostic factor for MFS (P = 0.005) and CSS (P = 0.04). Most patients with M protein that persisted for more than one year after RT were diagnosed with multiple myeloma within 2.2 years of treatment. CONCLUSIONS: Patients with M protein that persists for more than one year after RT should be monitored frequently and considered for standard chemotherapy followed by intensive consolidation therapy when they either develop symptoms or show an increasing M protein level.

Adult↗