Terry M. Therneau

Increased Risk of Monoclonal Gammopathy in First-Degree Relatives of Patients with Multiple Myeloma or Monoclonal Gammopathy of Undetermined Significance.

We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, >/= 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.

Effect of complete response on outcome following autologous stem cell transplantation for myeloma

We studied the effect of complete response (CR) among 126 consecutive patients who underwent stem cell transplantation (SCT) for myeloma. The CR rate with SCT was 33%. Median overall survival (OS) from diagnosis of myeloma was 56 months. OS following SCT was 22 months. Progression-free survival (PFS) was 12 months. OS was not different between patients who achieved CR and those who did not, median survival 25 vs 24 months, P = 0.5. Corresponding median times for PFS were 15 and 11 months, P = 0.2. The plasma cell labeling index (PCLI) was high (⩾1%) in 36% (high risk group) and was associated with poor OS and PFS (P < 0.001). Achieving CR did not influence OS or PFS in either the high or the low risk group. In contrast, OS and PFS were significantly influenced by high PCLI both in patients who achieved CR and those who did not. OS was poor (<30 months) in high risk patients regardless of CR status and in low risk patients who did not achieve CR, compared to low risk patients achieving CR (57 months), making them candidates for novel post-transplant treatment options. Outcome following SCT is dependent more on biological variables such as the PCLI than on CR status. Bone Marrow Transplantation (2000) 26, 979–983.

Autologous stem cell transplantation for relapsed and primary refractory myeloma

The aim of this study was to evaluate the effectiveness of autologous stem cell transplantation for patients with relapsed or primary chemotherapy-refractory myeloma. Seventy-five patients, 50 men and 25 women, ages 33–68 years (median, 53 years), who underwent transplantation for relapsed or primary refractory myeloma were studied. Patients underwent transplantation 5–88 months (median, 23 months) after diagnosis of myeloma. The time to transplantation was significantly shorter in patients with refractory disease than for those with relapsed myeloma (median, 8 and 32 months, respectively; P < 0.001). patients with primary refractory myeloma had a significantly lower plasma cell labeling index than those with relapsed disease (P = 0.008). There were no differences in overall and complete response rates between patients with primary refractory and relapsed disease. The median survival of the entire cohort from diagnosis was 53 months. Overall survival from transplantation among patients with relapsed myeloma receiving therapy, relapsed myeloma off therapy, and primary refractory myeloma was significantly different (P = 0.04), with median times of 12, 21 and 30 months, respectively. Progression-free survival also was different (P < 0.001), with median times of 7, 13, and 26 months, respectively. we conclude that overall and progression-free survival in patients with primary refractory myeloma appear better than in patients with relapsed disease and need further study.

Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma.

We compared the prognostic value of conventional cytogenetic analysis and established factors such as β2-microglobulin and plasma cell labeling index in 70 patients undergoing autologous blood cell transplantation for multiple myeloma. Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Factors studied were age, sex, β2-microglobulin, response to prior therapy, plasma cell labeling index, cytogenetic analysis, bone marrow plasma cell percentage, lactate dehydrogenase and C-reactive protein. Twenty-eight of 65 patients (43%) had abnormal marrow cytogenetics. Overall survival measured from transplantation was significantly better in patients with normal cytogenetics than in those with abnormal cytogenetics (median survival, 25 vs 12 months, P = 0.003). Progression-free survival was better, with median times of 12 vs7 months, respectively (P = 0.005); overall survival measured from the time myeloma was first diagnosed was also longer, with median survivals of 62 and 39 months, respectively (P = 0.001). Median plasma cell labeling index was 1.5% in patients with abnormal cytogenetics and 0.2% in those with normal cytogenetics (P < 0.001). abnormal bone marrow cytogenetics predict poor survival after blood cell transplantation for myeloma. there is a significant correlation between abnormal cytogenetics and high plasma cell labeling index, suggesting that certain cytogenetic abnormalities may offer a proliferative advantage to myeloma cells.

Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma

Summary:The purpose of this study was to determine the effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. We performed a retrospective review of 67 patients newly diagnosed with multiple myeloma at Mayo Clinic and treated with a single regimen prior to stem cell transplantation between January of 2000 and September of 2001. Stem cells were collected from 24 patients who received thalidomide, 200 mg/day, with dexamethasone as initial therapy before stem cell collection. These patients were compared with 43 control patients seen during the same period who had received only one previous regimen before stem cell collection and transplantation. The cumulative thalidomide dose before stem cell collection was 17 000 mg over a median of four cycles (range, 2–7 cycles). The thalidomide and control groups were not significantly different in their baseline characteristics, number of stem cells collected, time to collection, or time to engraftment of neutrophils or platelet count of 50 000/μl. Time to platelet count of 20 000/μl was delayed by a median of 4 days (P=0.008), but platelet transfusion requirements did not differ (P=0.95). We concluded that thalidomide does not substantially affect peripheral cell mobilization or engraftment.

Beta2-microglobulin and bone marrow plasma cell involvement predict complete responders among patients undergoing blood cell transplantation for myeloma.

We studied the prognostic value of clinical and laboratory variables, measured before blood cell transplantation, in predicting complete response among patients undergoing autologous blood cell transplantation for relapsed or primary refractory myeloma. Sixty-seven patients who underwent transplantation for relapsed or primary refractory myeloma were studied. The overall response rate was 90%, and the complete response rate was 33%. Low β2-microglobulin (⩽2.7 mg/l) was associated with a significantly better complete response rate compared with high levels (54 vs19%, P = 0.002). Similarly, the complete response rate was 39% when the bone marrow plasma cell percentage was low (<40%) and 21% with greater involvement (P = 0.04). Complete response rate was 50% when β2-microglobulin and bone marrow plasma cell percentage were low, 36% if either was high, and 12% when both were high (P = 0.01). Median survival measured from initial diagnosis of myeloma was 51 months. Overall survival after transplantation was better among responders who achieved complete response than those who did not: median survival, 24 vs 11 months, P = 0.04 (log-rank) and 0.009 (Gehan–Wilcoxon). Attainment of a complete response independently predicted better survival in a multivariate analysis. β2-Microglobulin and bone marrow plasma cell percentage predict complete responders among patients undergoing transplantation for myeloma.