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• W2092502877 abstract "Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients ≤40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients ≤40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients ≤40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM. Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients ≤40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients ≤40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients ≤40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM. Multiple myeloma (MM) is a malignant plasma cell disorder primarily of the elderly, with a peak incidence between 60 and 70 years of age [1Kyle R.A. Long term survival in multiple myeloma.N Engl J Med. 1983; 30: 314-316Crossref Scopus (131) Google Scholar, 2Kyle R.A. Gertz M.A. Witzig T.E. et al.Review of 1072 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1602) Google Scholar]. It is uncommon in persons younger than 40 years, representing only 2% of all patients diagnosed with MM [2Kyle R.A. Gertz M.A. Witzig T.E. et al.Review of 1072 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1602) Google Scholar, 3Blade J. Kyle R.A. Griepp P.R. Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years.Br J Haematol. 1996; 93: 345-351Crossref PubMed Scopus (162) Google Scholar]. Younger age has been reported to correlate with improved survival, and has been recognized as an important prognostic factor [2Kyle R.A. Gertz M.A. Witzig T.E. et al.Review of 1072 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1602) Google Scholar, 4Ludwig H. Durie B.G.M. Bolejack V. et al.Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group.Blood. 2008; 111: 4039-4047Crossref PubMed Scopus (145) Google Scholar, 5Mileshkin L. Biagi J.J. Mitchell P. et al.Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age.Blood. 2003; 102: 69-77Crossref PubMed Scopus (112) Google Scholar, 6Garcia-Sanz R. Gonzalez-Fraile M.I. Mateo G. et al.Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patients.Int J Cancer. 2004; 112: 884-889Crossref PubMed Scopus (48) Google Scholar, 7Kumar S.K. Rajkumar S.V. Dispenzieri A. et al.Improved survival in multiple myeloma and the impact of novel therapies.Blood. 2008; 111: 2516-2520Crossref PubMed Scopus (1805) Google Scholar]. Chromosomal patterns have been analyzed in patients <45 years of age and compared to older cohorts, and no significant difference between the groups have been found, suggesting that MM in young patients does not represent a distinct biologic entity and does not explain the positive prognostic factor [8Sagaster V. Kaufmann H. Odelga V. et al.Chromosomal abnormalities of young multiple myeloma patients (<45 yr) are not different from those of other age groups and are independent of stage according to the international staging system.Eur J Haematol. 2007; 78: 227-234Crossref PubMed Scopus (14) Google Scholar]. MM in young patients was initially thought to have a more indolent course with atypical presentations such as multiple solitary or extramedullary plasmacytomas, increased osteolytic lesions, lower serum or urinary monoclonal proteins, and few or no plasma cells in the bone marrow [9Hewell G.M. Alexanian R. Multiple myeloma in young persons.Ann Intern Med. 1976; 84: 441-443Crossref PubMed Scopus (69) Google Scholar, 10Lazarus H.M. Kellermeyer R.W. Aikawa M. Herzig R.H. Multiple myeloma in young men: clinical course and electron microscopic studies of bone marrow plasma cells.Cancer. 1980; 46: 1397-1400Crossref PubMed Scopus (27) Google Scholar, 11Geetha N. Jayaprakash M. Rekhanair A. Ramachandran K. Plama cell neoplasms in young.Br J Radiol. 1999; 72: 1012-1015PubMed Google Scholar]. However, Blade and colleagues [3Blade J. Kyle R.A. Griepp P.R. Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years.Br J Haematol. 1996; 93: 345-351Crossref PubMed Scopus (162) Google Scholar] disputed this by publishing a series of 72 patients younger than 40 years of age with MM who had presenting features and response to therapy similar to those reported in series of MM with older patients. Despite the similarities, a median survival of 54 months was observed, which suggested improved survival compared to the general MM population, which had an overall survival (OS) of 2-3 years at that time [12Blade J. San Miguel J.F. Alcala A. et al.Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.J Clin Oncol. 1993; 11: 1165-1171PubMed Google Scholar, 13Greipp P.R. Lust J.A. O'Fallon WM, Katzmann JA, Witzig TE, Kyle RA. Plasma cell labeling index and beta 2 microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma.Blood. 1993; 81: 3382-3387PubMed Google Scholar, 14Salmon S.E. Tesh D. Crowley J. et al.Chemotherapy is superior to sequential hemibody irradiation for remission consolidation in multiple myeloma: a Southwest Oncology Group study.J Clin Oncol. 1990; 8: 1575-1584PubMed Google Scholar]. In that cohort, only 9 patients underwent autologous stem cell transplantation (ASCT), of which only 3 had upfront ASCT. As ASCT remains the standard of care in eligible patients as upfront therapy, this may not reflect the true prognosis of these patients undergoing this modality of treatment. Indeed, 2 randomized controlled trials comparing conventional chemotherapy to high-dose chemotherapy with ASCT rescue as initial therapy in MM have shown improvement in event free survival (EFS) and OS in patients under the age of 65 years [15Attal M. Harousseau J.L. Stoppa A.M. et al.A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma.N Engl J Med. 1996; 335: 91-97Crossref PubMed Scopus (2569) Google Scholar, 16Child J.A. Morgan G.J. Davies F.E. et al.High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.N Engl J Med. 2003; 348: 1875-1883Crossref PubMed Scopus (1574) Google Scholar]. More recently, patients younger than 50 years of age with MM were compared to patients 50 years and older who underwent treatment with either conventional chemotherapy or upfront ASCT and found that young patients had a significantly longer survival with either treatment modality [4Ludwig H. Durie B.G.M. Bolejack V. et al.Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group.Blood. 2008; 111: 4039-4047Crossref PubMed Scopus (145) Google Scholar]. The standard of care at our institution is to offer upfront ASCT for all suitable patients under the age of 65 years diagnosed with MM. Given that young patients rarely have contraindications to ASCT and may be able to better tolerate high-dose therapy, almost all patients ≤40 years of age undergo ASCT. The objective of this study is to describe presenting features and outcomes of patients ≤40 years of age with MM who undergo ASCT as first-line treatment and compare OS and PFS to an older cohort. Patients were identified from the Princess Margaret Hospital (PMH) ASCT database. All patients aged 40 years or less at the time of diagnosis of MM that underwent ASCT from January 1, 1990, to August 1, 2007, were included in the study. PMH is a referral center for peripheral hospitals, and presenting data was used from the referring centers when available. Only patients who underwent upfront ASCT for the diagnosis of MM were included. Patients who had undergone ASCT as salvage therapy and patients who had received chemotherapy for smoldering myeloma or solitary plasmacytoma were excluded from the study. This patient group was compared to patients aged 41-65 years who were identified by the PMH ASCT database, and had also underwent upfront ASCT. Response to treatment and progression were assessed using the European Blood and Bone Marrow Transplantation (EBMT) criteria [17Blade J. Samson D. Reece D. et al.Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation.Br J Haematol. 1998; 102: 1115-1123Crossref PubMed Scopus (1474) Google Scholar]. Response to transplantation was taken at the closest follow up visit to 100 days post-ASCT. Anemia was defined as a hemoglobin <12 g/dL; hypercalcemia defined as a corrected calcium ≥2.75 mmol/L; and renal failure as a creatinine ≥177 μmol/L. Plasma cell leukemia (PCL) was defined as the presence of >20% plasma cells in peripheral blood and an absolute plasma cell count more than 2 × 109/L [18Grogan T.M. Muller-Hermelink H.K. Van C.B. Harris N.L. Kyle R.A. World Health Organization classification tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, France2001Google Scholar]. Time of neutrophil engraftment was defined as first of 2 consecutive days with an absolute neutrophil count (ANC) >0.5 × 109/L. Time of platelet engraftment was defined as first of 3 consecutive days with platelets >20 × 109/L and platelet transfusion independent for 7 days. OS was measured from date of diagnosis and from date of ASCT to date of last follow-up or death. PFS was calculated for all patients from date of ASCT to time of relapse, death, or date the patient was last known to be in remission. Curves for OS and PFS were plotted according to the method of Kaplan and Meier, and were compared to patients 41-65 years of age by the log-rank test. For all tests, a 2-sided P-value of ≤.05 was considered statistically significant. Calculations were performed using SPSS/PC (SPSS Inc., Chicago IL). Forty-three patients aged ≤40 years at time of diagnosis of MM were identified. Five patients were excluded for undergoing salvage ASCT or ASCT >18 months from diagnosis. Thirty-eight patients were included in the analysis. All patients identified through the ASCT database had presented with MM requiring treatment; none of the young patients in this study presented with monoclonal protein of undetermined significance (MGUS), smoldering myeloma, or solitary plasmacytomas that had progressed to MM. The median age was 37.2 years (range: 29.3-40.1 years), and 23 (61%) were males. Six hundred eight patients in the comparator group were identified with a median age of 56.4 years (range: 41.1-65.5 years), and 365 (60%) were males. Table 1 shows the distribution according to the M-protein type in young patients. A majority had IgG MM (53%), followed by light chain (LC) MM at 21%. The remainder of patients had IgA or IgD MM at 18% and 8%, respectively. Four patients (11%) had evidence of PCL at diagnosis. A majority of patients had κ LC type (74%). No patients had evidence of systemic amyloidosis (AL).Table 1Characteristics of Patients ≤40 Years of Age with MMCharacteristicAge—year Median37.2 Range29.3-40.1Males—no. of patients (%)23 (61)Monoclonal protein—no.of pts (%)Light chainsκλ IgG20 (53)173 Light chain8 (21)44 IgA7 (18)61 IgD3 (8)12Plasma cell leukemia—no. of patients (%)4 (11)MM indicates multiple myeloma. Open table in a new tab MM indicates multiple myeloma. Laboratory features at presentation of patients ≤40 years of age are shown in Table 2. Sixty-seven percent of young patients were anemic. Twenty-five percent of young patients had renal failure at time of diagnosis compared to 16% in the older cohort. The rate of hypercalcemia was similar in the young and older cohorts at 23% and 22%, respectively. The rate of ≥30% plasma cells in bone marrow was comparable at 72% in the young cohort and 74% in the older cohort. Bence Jones proteinuria was more common in the younger cohort at a rate of 81% compared to 51% in the older cohort. A majority of young patients (76%) and older patients (74%) had radiologic evidence of bone disease at diagnosis. In patients ≤40 years of age, 3 patients (8%) presented with spinal cord compression, and 16 (42%) patients underwent palliative radiation for bone disease prior to ASCT. Of the 21 patients in the young cohort that staging according to the International Staging System (ISS) could be obtained, 48% of patients were stage 1 at diagnosis. Ten young patients had cytogenetics reported, of which 9 had abnormal cytogenetics. Three patients had deletion of chromosome 13, 3 had t(11;14), and 1 patient had both.Table 2Laboratory Data at Time of Diagnosis of MM in Patients ≤40 Years of AgeFactorNo. of PatientsMedianRangeLimitHemoglobin (g/dL)3310.439-147<12, 67%Calcium (mmol/L)312.451.99-3.67≥2.75, 23%Creatinine (μmol/L)329353-894≥177, 25%Bone marrow plasma cells (%)32654-100≥30%, 72%Albumin (g/L)2439.522-48<38, 38%β-2-microglobulin (μmol/L)2017231-1100>300, 20%Bence Jones protein31Present, 81%MM indicates multiple myeloma. Open table in a new tab MM indicates multiple myeloma. Details of the transplantation for patients aged ≤40 years of age are summarized in Table 3. As induction chemotherapy, 66% of patients received vincristine, adriamycin, and dexamethasone (VAD), with a median of 4 cycles (range: 2-7), 13% received high-dose dexamethasone alone on a VAD schedule, and 13% received melphalan and prednisone (MP). Two patients received both MP and VAD as initial therapy.Table 3ASCT Parameters of Patients ≤40 Years of ageFactorNo. of Patients (%)MedianRangeFirst line induction therapy (n = 38) VAD25 (66)4 cycles2-7 Dexamethasone on a VAD schedule5 (13) Melphalan and Prednisone5 (13)Patients receiving ≥2 lines of induction therapy (n = 38)16 (42)Patients that progressed while waiting for ASCT (n = 38)5 (13)Cyclophosphamide and G-CSF mobilization (n = 36)33 (87)Conditioning Regimen (n = 38) Melphalan 200 mg/m224 (63) Melphalan, VP16, ±TBI10 (26) Busulfan and cyclophosphamide4 (11)Type of SCT (n = 38) Peripheral blood37 (97) Peripheral blood + bone marrow1 (3)CD34+ × 106 cells/kg (n = 29)7.523.0-73.3Time to ASCT from diagnosis, months (n = 38)8.54.8-17.9VAD indicates vincristine, adriamycin, and dexamethasone; ASCT, autologous stem cell transplantation; SCT, stem cell transplantation; G-CSF, granulocyte-colony stimulating factor; TBI, total body irradiation.∗2 pts had planned Melphalan and Prednisone followed by VAD. Open table in a new tab VAD indicates vincristine, adriamycin, and dexamethasone; ASCT, autologous stem cell transplantation; SCT, stem cell transplantation; G-CSF, granulocyte-colony stimulating factor; TBI, total body irradiation. ∗2 pts had planned Melphalan and Prednisone followed by VAD. Eighty-seven percent of patients received cyclophosphamide (Cy) and granulocyte-colony stimulating factor (G-CSF) as mobilizing agents. Sixty-three percent of patients were conditioned with melphalan (Mel) 200 mg/m2 in either 1 dose or 2 doses of 100 mg/m2. Twenty-six percent of patients received Mel 160 mg/m2, VP16 60 mg/kg, ± total body irradiation (TBI), and 11% received busulfan (Bu) and Cy at a total dose of 14 mg/m2 and 120 mg/kg, respectively, as part of the Cell Pro Study [19Vescio R. Schiller G. Stewart A.K. et al.Multicenter phase III trial to evaluate CD34+ selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.Blood. 1999; 93: 1858-1868PubMed Google Scholar]. All patients received peripheral blood stem cells (PBSCs), with 1 patient receiving bone marrow stem cells in addition to their PBSCs. Median infused CD34+ cell dose was 7.52 × 106 cells/kg (range: 3-73.3). Median time to ASCT from date of diagnosis was 8.5 months (range: 4.8-17.9 months). Eleven percent of patients had a complete remission (CR) after first-line induction that increased to 13% at the time of ASCT, and 55% had a partial remission (PR) following induction, which also increased to 63% at the time of ASCT Table 4.Table 4Response Rates in Patients with MM Undergoing Upfront ASCT≤ 40 Years, n = 38 (%)41-65 Years, n = 192 (%)ResponseFollowing First Induction TreatmentStatus Prior to ASCTPost-ASCTPost-ASCTCR4 (11)5 (13)11 (29)33 (17)PR21 (55)24 (63)19 (50)126 (66)MR7 (18)7 (18)2 (5)4 (2)SD3 (8)2 (5)3 (8)15 (8)PD3 (8)02 (5)8 (4)MM indicates multiple myeloma, ASCT, autologous stem cell transplantation; CR, complete response; PR, partial response; MR, minimal response; SD, stable disease; PD, progressive disease. Open table in a new tab MM indicates multiple myeloma, ASCT, autologous stem cell transplantation; CR, complete response; PR, partial response; MR, minimal response; SD, stable disease; PD, progressive disease. Table 5 illustrates safety endpoints following ASCT. Median time to neutrophil engraftment was 11 days (range: 9-18 days), and median time to platelet engraftment was 11 days (range: 6-15 days). One patient failed to engraft platelets, and 2 patients’ platelets never fell below 20 × 109/L. Of the 22 patients in which transfusion data was available, 41% and 55% required packed red blood cells (PRBC) and platelet transfusions, respectively. Median PRBC transfusions was 2 units (range: 2-4), and median platelet transfusions was 5 units (range: 5-15). The rate of febrile neutropenia was 82% (28 of 34 patients). Median length of hospital admission from date of ASCT was 15 days (range: 11-43 days).Table 5Safety Endpoints in Patients ≤40 years of Age with MM Undergoing Upfront ASCTEndpointNo. of Patients (%)MedianRangeNeutrophil engraftment (n = 32)32 (100)11 days9-18Platelet engraftment (n = 31)30 (97)11 days6-15PRBC transfusions (n = 22)9 (41)2 units2-4Platelet transfusions (n = 22)12 (55)5 units5-15Febrile Neutropenia (n = 34)28 (82)Days of hospitalization (n = 35)1511-43MM indicates multiple myeloma; PRBC, packed red blood cells; ASCT, autologous stem cell transplantation. Open table in a new tab MM indicates multiple myeloma; PRBC, packed red blood cells; ASCT, autologous stem cell transplantation. Post-ASCT, 49% of patients received maintenance therapy. Regimens varied from combinations of interferon, prednisone, dexamethasone, and thalidomide. Five (13%) of the patients went on to tandem ASCT. The median time to best response following ASCT was recorded at 3 months post-ASCT (range: 31-152). Table 4 illustrates response rates post ASCT. In the young cohort, 29% achieved a CR, 50% a PR, 5% a minimal response (MR), 8% had stable disease (SD), and 5% had progressive disease (PD). Following tandem ASCT, 1 patient with MR and 1 patient with PR obtained a CR. Seventeen percent of patients aged 41-65 achieved a CR, 66% a PR, 2% an MR, 8% had SD, and 4% had PD. The median duration of follow-up among survivors was 53 months (range: 12-198 months). Table 6 displays study outcomes. Median OS from date of diagnosis in patients ≤40 years of age was 81.4 months (95% CI: 49.0, 113.1). Although there was a trend to shortened survival, there was no difference in median OS from date of ASCT when patients ≤40 years of age were compared to the cohort of patients 41-65 years of age (68.1 months [95% CI: 39.0, 97.2] versus 80.7 months [95% CI: 68.1, 93.4], P = .90), nor was there a difference in median PFS from date of ASCT (22.0 months [95% CI: 16.1, 28.0] versus 26.9 months [95% CI: 24.0, 29.8]; P = .66) (Figure 1, Figure 2) . The actuarial survival of patients ≤40 years of age at 5 and 10 years from date of ASCT was 60% and 43%, respectively, and PFS at 5 and 10 years was 31% and 25%, respectively.Table 6Study OutcomesEndpoint≤40 Years Months (95% CI) n = 3841-65 Years Months (95% CI) n = 608P-ValueMedian OS from date of diagnosis81.4 (49.0, 113.1)Median OS from ASCT68.1 (39.0, 97.2)80.7 (68.1, 93.4).9Median PFS from ASCT22.0 (16.1, 28.0)26.9 (24.0, 29.8).66Median OS from ASCT CR + PR (n = 30)79.0 (51.4, 106.6).2 MR, SD, PD (n = 7)42.6 (0, 88.6)Median PFS from ASCT CR+PR (n = 30)30.9 (5.2, 56.5).02 MR, SD, PD (n = 7)8.0 (5.2, 10.9)ASCT indicates autologous stem cell transplantation; OS, overall survival; PFS, progression free survival; CR, complete response; PR, partial response; MR, minimal response; SD, stable disease; PD, progressive disease; CI, confidence interval. Open table in a new tab Figure 2Kaplan-Meier estimates of PFS in patients with MM ≤40 years of age compared to patients aged 41-65 years who underwent upfront ASCT.View Large Image Figure ViewerDownload Hi-res image Download (PPT) ASCT indicates autologous stem cell transplantation; OS, overall survival; PFS, progression free survival; CR, complete response; PR, partial response; MR, minimal response; SD, stable disease; PD, progressive disease; CI, confidence interval. Subgroup analysis, revealed that, although not statistically significant, there was a trend to improved median OS of patients ≤40 years of age with ISS stage 1 at diagnosis compared those >1 (85.6 versus 33.4 months; P = .22). There was no statistically significant difference in median OS from date of ASCT if young patients were either in CR or PR post-ASCT compared to MR, SD, and PD (79.0 versus 42.6 months; P = .20), whereas those young patients that achieved CR or PR post-ASCT appreciated a statistically significant longer PFS (30.9 versus 8.0 months, P = .02). One patient ≤40 years of age died from sepsis within 100 days of ASCT, yielding a treatment-related mortality (TRM) of 2.6%. The older cohort experienced a similar TRM, with 14 deaths within 100 days of ASCT (2.3%). Main causes of death in the young cohort were from PD and infection (Table 7).Table 7Causes of Death in 38 Patients ≤40 Years of Age with MMCauseNo. of PatientsMyeloma progression7Infection5Aspiration pneumonia1Hemorrhagic cystitis/renal failure1Pulmonary and brain hemorrhages1Unknown2MM indicates multiple myeloma. Open table in a new tab MM indicates multiple myeloma. This is the first series to report that very young patients with MM undergoing upfront ASCT do not have superior prognosis compared to an older cohort. All patients in this study presented with MM without a prior plasma cell disorder. Presenting features of anemia and hypercalcemia in this patient population were comparable to the general population with MM [2Kyle R.A. Gertz M.A. Witzig T.E. et al.Review of 1072 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1602) Google Scholar] and to reported rates in patients <40 years of age [3Blade J. Kyle R.A. Griepp P.R. Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years.Br J Haematol. 1996; 93: 345-351Crossref PubMed Scopus (162) Google Scholar]. In our study, IgG MM was found in more than half the patients, which again, is consistent with the general MM population; however, as previously reported in young patients, LC MM occurred at a higher rate than IgA MM, unlike the older population, and there was an increase in IgD MM at 8% compared to reported rate of 2% [20Ameis A. Ko H.S. Pruzanski W. M components-a review of 1242 cases.Can Med Assoc J. 1976; 114: 889-895PubMed Google Scholar, 21Hobbs J.R. Immunochemical classes of myelomatosis. Including data from a therapeutic trial conducted by a Medical Research Council working party.Br J Haematol. 1969; 16: 599-606Crossref PubMed Scopus (83) Google Scholar]. IgD MM has been commonly associated with renal failure, and a majority have Bence Jones proteinuria [22Blade J. Kyle R.A. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia.Hematol Oncol Clin North Am. 1999; 13: 1259-1272Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar]; only 1 of the 3 patients with IgD MM had renal failure at diagnosis, but all had Bence Jones proteinuria. Chromosome 13 deletion, a common chromosomal abnormality in MM that has been associated with shortened PFS following ASCT [23Desikan R. Barlogie B. Sawyer J. et al.Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.Blood. 2000; 95: 4008-4010PubMed Google Scholar], was found in one-third of our patients, again similar to the reported rate in various age groups [8Sagaster V. Kaufmann H. Odelga V. et al.Chromosomal abnormalities of young multiple myeloma patients (<45 yr) are not different from those of other age groups and are independent of stage according to the international staging system.Eur J Haematol. 2007; 78: 227-234Crossref PubMed Scopus (14) Google Scholar]. Despite the similarities to the general MM population, a few clinical parameters suggest that MM in young patient may present more aggressively. There was a high rate of Bence Jones proteinuria at 81%, and a high rate of renal failure with 25% of patients having a creatinine ≥177 μmol/L. The rate of renal failure was similar to the report by Blade and colleagues in patients <40 years of age [3], but higher than those aged 41-65 years in our series at 16% and previously reported in patients younger than 50 years of age at 15% [4Ludwig H. Durie B.G.M. Bolejack V. et al.Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group.Blood. 2008; 111: 4039-4047Crossref PubMed Scopus (145) Google Scholar]. There was also an increased risk of PCL at 11% compared to the reported incidence of 2%-4% [24Dimopoulos M.A. Palumbo A. Delasalle K.B. et al.Primary plasma cell leukaemia.Br J Haematol. 1994; 88: 754-759Crossref PubMed Scopus (157) Google Scholar, 25Garcia-Sanz R. Orfao A. Gonzalez M. et al.Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetics characteristics.Blood. 1999; 93: 1032-1037PubMed Google Scholar, 26Noel P. Kyle R.A. Plasma cell leukemia: an evaluation of response t" @default.
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• W2092502877 date "2009-06-01" @default.
• W2092502877 modified "2023-10-18" @default.
• W2092502877 title "Age 40 Years and Under Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transmplant" @default.
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