Autologous hematopoietic cell transplantation (AHCT) is a standard of care in multiple myeloma (MM) patients aged <65 years. To understand age-related trends in utilisation and outcome of AHCT, we analysed 53 675 MM patients who underwent a first AHCT in 31 European countries between 1991 and 2010. The number of patients undergoing AHCT increased for all age groups (<40, 40–49, 50–59, 60–64, 65–69 and ⩾70 years) throughout the observation period. The highest increase was observed for patients aged ⩾65 years, who accounted for 3% of AHCTs in 1991–1995 and for 18.8% of AHCTs in 2006–2010. Risk factors associated with survival over the entire observation period (P<0.001) were calendar period, remission status at AHCT, gender, disease duration before AHCT and age. Survival improved considerably more in older than in younger patients in recent years. In 2006–2010, median 2- and 5-year post-transplant survival ranged from 85.9 and 61.5% in patients <40 years to 80.2 and 49.7% in those ⩾70 years. All-cause day-100 mortality decreased throughout the observation period to ⩽2.4% for all age groups in 2006–2010. The results of this study demonstrate increased utilisation and safety of AHCT with improved post-transplant survival particularly in elderly MM patients in recent years in Europe.
Multiple myeloma (MM) accounts for 10–13% of haematological malignancies and has a median age at diagnosis of 65–70 years.1, 2, 3, 4 In the 1980s, ground-breaking studies identified high-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) as an effective treatment option.5, 6, 7, 8, 9, 10 Subsequently, two randomised trials in patients under the age of 65 years demonstrated the superiority of high-dose chemotherapy and AHCT over standard chemotherapy.11, 12 AHCT has also been shown to be feasible in selected older patients.13, 14, 15, 16, 17, 18, 19, 20, 21, 22 However, intermediate-dose melphalan followed by AHCT was inferior to the combination of standard-dose melphalan with prednisolone and thalidomide in patients aged 65–75 years in the randomised IFM99-06 trial.23 Consequently, AHCT has not been recommended as a standard of care for MM patients who are ⩾65 years of age.24, 25, 26, 27
Large single-centre and population-based studies conducted in the US and in Europe have shown that survival of MM patients has improved considerably in recent years compared with past decades.28, 29, 30, 31, 32, 33, 34 However, improvements in survival were predominantly seen in younger patients, with the exception of very recent US-based studies.28, 29, 30, 31, 32, 33, 34 The reasons for these trends are not fully understood. Although some studies attributed improvements in survival to the introduction of drugs with novel mechanisms of action (‘novel agents’), others associated better survival predominantly with AHCT, or trial participation.28, 29, 30, 31, 32, 33, 34
AHCT is an intensive and costly procedure. On the other hand, AHCT can result in prolonged periods of therapy-free time that decrease the need for other economically challenging therapies. Hence, it is of clinical and economic importance to understand trends in utilisation and outcome of AHCT for MM. Given that most MM patients are >65 years, the cutoff age from which AHCT is not generally recommended, it is of particular relevance to consider these trends in relation to patient age. We therefore analysed first AHCT for MM in Europe that were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 20-year time period.
Patients and methods
The EBMT Registry
The EBMT is a nonprofit organisation that was established in 1974 and maintains a patient database known as the EBMT Registry, which encompasses data on hematopoietic cell transplant (HCT) procedures for all indications. The EBMT has a single centralised database where all the data requested through the standard data-collection forms are stored. The data are submitted when 100 days have elapsed from the date of transplant, or when the patient dies, whichever comes first. Follow-up is otherwise indefinite. All EBMT member centres need to forward these data to retain full membership. The data are stored in an SQL Server database, housed in the Leiden University Medical Centre, Leiden, The Netherlands. All centres inside and outside the European Union must obtain informed consent from their patients before the data can be submitted to the EBMT. Informed consent to data utilisation was obtained as previously described.35
Patients included in this study were reported to the EBMT Registry for undergoing a first AHCT for treatment of MM in a European country (including Turkey) between 01 January 1991 and 31 December 2010. Thus, patients were not included if they had a prior allogeneic HCT, or had their first AHCT for a disease other than MM. Patients were grouped into four 5-year calendar periods by time of first AHCT (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and into six age groups based on their age at the time of AHCT (<40, 40–49, 50–59, 60–64, 65–69 and ⩾70 years).
OS was calculated using the Kaplan–Meier method. OS was measured in months and defined as the time from the date of AHCT until date of death or last follow-up. Variables included in a proportional hazards regression analysis were age group, calendar period, gender, remission status at AHCT and disease duration before AHCT. Remission status was defined as previously described.36, 37
A total of 53 675 patients from 31 countries and 497 centres was reported to the EBMT for undergoing a first AHCT for treatment of MM between 1991 and 2010. The number of patients undergoing a first AHCT increased throughout all four calendar periods (Table 1), with almost half of all recorded AHCTs (45.6%) performed in 2006–2010. The median age at AHCT increased from 52.8 years in 1991–1995 to 59 years in 2006–2010 (Table 1). BM was seldom used as the stem cell source after 1991–1995 (Table 1). The proportion of patients who received their first AHCT within 12 months from diagnosis increased sharply from 1991–1995 to 1996–2000 and remained stable during the two most recent calendar periods (Table 1). There was a noticeable increase in patients transplanted in >PR in 2006–2010 compared with previous calendar periods (Table 1).
The absolute number of patients undergoing a first AHCT for MM increased for all age groups throughout the observation period (Table 2). The highest proportional increase over time was observed for patients aged 65–69 years and ⩾70 years. These two age groups together accounted for 3% of AHCTs performed in 1991–1995 and for 18.8% of AHCTs performed in 2006–2010. Age groups showed small but statistically significant differences in gender distribution and remission status at AHCT, with a higher proportion of male patients and patients transplanted in >PR in the younger age groups (Table 2). The proportion of patients who underwent AHCT within 1 year from diagnosis decreased moderately with increasing age, from 78.5% in patients <40 years to 70.8% in those aged ⩾70 years (Table 2). Utilisation of early second AHCT ⩽6 months after the first transplant, which generally indicates a tandem-AHCT approach, was uncommon in 1991–1995 and peaked in 2001–2005 in all age groups. Although early second AHCTs were used less in 2006–2010 in all age groups, patients aged ⩾70 years showed the smallest decrease and represented the age group with the highest rate of early second transplants in this calendar period (Table 2).
Survival rates after AHCT increased for all age groups from 1991–1995 to 2006–2010. Only two patients aged ⩾70 years underwent AHCT in 1991–1995 and died after 10 and 16 months, respectively, from progressive disease. We observed considerable differences between age groups in the changes of 2-year and 5-year survival after AHCT (Table 3 and Figure 1). The greatest improvement in 2-year survival was observed in patients aged 65–69 years (27.6%; from 55.3% in 1991–1995 to 82.9% in 2006–2010). The improvement in 2-year survival progressively decreased with every age bracket and was smallest in patients aged <40 years (3.7%; from 82.2% in 1991–1995 to 85.9% in 2006–2010). Consequently, the difference in 2-year survival between age groups decreased from a maximum of 27.9% in 1991–1995 (between patients aged <40 and 65–69 years) to 5.7% in 2006–2010 (between patients aged <40 and ⩾70 years). Of note, a 2-year survival of >80% was observed only in patients aged <40 years in the first two calendar periods, in patients up to the age of 64 years in 2001–2005, and in all age groups in 2006–2010.
The improvement in 5-year survival (Table 3 and Figure 1) was most pronounced in patients aged 60–64 years (26%; from 32.8% in 1991–1995 to 58.8% in 2006–2010). The smallest improvement from 1991–1995 to 2006–2010 was seen in patients <40 years (7.5%). In this age group, there was a trend towards decreasing 5-year survival in 2006–2010 compared with both 2001–2005 and 1996–2000. Five-year survival in patients aged 40–49 years was also slightly lower in 2006–1010 compared with 2001–2005. The difference in 5-year survival between age groups decreased from 21.2% in 1991–1995 (between patients <40 and 60–64 years) and 29.9% in 1996–2000 (between patients <40 and ⩾70 years), respectively, to 13.1% in 2006–2010 (between patients 40–49 and ⩾70 years).
Over the entire observation period, factors associated with survival after AHCT in a proportional hazards regression analysis were patient age, calendar period, remission status at AHCT, gender and time between diagnosis and AHCT (Table 4). The relative risk of death increased progressively for every age bracket compared with the youngest patient group (<40 years). When compared with AHCTs performed in 1991–1995, the risk of dying decreased in every subsequent 5-year calendar period. Compared with AHCT in >PR, the relative risk of death was also higher in patients undergoing AHCT in PR and particularly in
There are three key findings in the present study. First, utilisation of AHCT for MM in Europe continued to increase in recent years, and increased predominantly in older patients. Second, survival after AHCT improved more in older than in younger patients. Third, early deaths after AHCT decreased to very low levels in all age groups.
Our findings demonstrate that the use of AHCT for MM continued to increase in Europe in recent years, and increased particularly in older patients. These observations are compatible with those reported by the Centre for International Blood and Marrow Transplant Research for the US and Canada.38, 39 Costa et al.39 found that the number of AHCTs performed exceeded new MM cases in all age categories between 1995 and 2010, whereas the median age at AHCT increased from 54 to 59 years. McCarthy et al.38 showed that the rate of AHCT for MM increased almost fivefold between 1994 and 2005. Together with these data from the US and Canada, the European data presented here indicate that, rather than supplanting AHCT, availability of novel agents has contributed to a further increase in the utilisation of AHCT in recent years. One possible explanation for this is that more patients were able to proceed to AHCT, because induction therapy with novel agents resulted in better responses and fewer treatment failures. This view is compatible with our observation that significantly more patients underwent AHCT in >PR in 2006–2010 compared with previous calendar periods. However, as the EBMT database does not consistently record pre- and post-transplant treatment, we were unable to formally test the impact of novel drugs on utilisation, or outcome, of AHCT in recent years.
Another major finding of this study is that survival after AHCT improved considerably more in older than in younger patients, resulting in a substantial narrowing of the gap in post-transplant survival between age groups in recent years. In particular, the 2-year survival after AHCT was similar for all age groups in the most recent calendar period, with a 2-year post-transplant survival of >80% even in patients aged ⩾70 years. These observations are compatible with those reported by the Centre for International Blood and Marrow Transplant Research, who observed an adjusted 2-year survival rate of 84% for all patients transplanted in 2005–2010.39 In contrast to the European data presented here, the Centre for International Blood and Marrow Transplant Research did not find a reduced risk of death after AHCTs performed in 2005–2010 compared with 2000–2004.39 However, the risk of dying in the most recent periods was lower than in 1995–1999, confirming earlier findings on patients transplanted between 1995 and 2005.38, 39 The EBMT data presented here provide evidence that post-transplant survival continued to improve in the most recent calendar period in the context of European healthcare systems and approaches to the treatment of MM. Furthermore, the data show for the first time that post-transplant survival has increased considerably more in older than in younger patients. The observations therefore have important clinical and economic implications, given that AHCT is not generally considered a standard of care in MM patients aged ⩾65 years.24, 25, 26, 27 This cutoff age is largely based on the findings of the IFM99–06 trial, in which intermediate-dose melphalan followed by AHCT was inferior to melphalan–prednisolone–thalidomide in patients aged 65–75 years.23 However, several studies have shown that AHCT is feasible, and can be an effective treatment option, in selected elderly MM patients.13, 14, 15, 16, 17, 18, 19, 20, 21, 22 In particular, it is worth considering a recent study from the Mayo Clinic in which AHCT was associated with improved survival only in patients aged >65 years, not in patients aged ⩽65 years. The data presented here show that, although age was a risk factor for death throughout the observation period, this was not limited to the oldest patients but applied to all age groups when compared with the very youngest patients. Similarly, all-cause mortality at day 100 after AHCT was higher in older than in younger patients throughout the study period, but without a clear cutoff between age groups. In fact, all-cause day-100 mortality was <2.5% even in patients aged ⩾70 years in the most recent calendar period. This finding is relevant as it indicates that treatment-related mortality across transplant centres is low in selected older patients. Our data therefore highlight the arbitrary nature of the 65-year cutoff that is commonly used to recommend AHCT as a standard of care. Another relevant finding of this study is that 5-year survival of patients aged <40 and 40–49 years appears to have decreased in recent years. Although the lack of information on pre- and post-transplant treatment regimens precludes the identification of the causes for the development from this study, the findings warrant a close follow-up of the data.
It is important to note that we found male patients to be associated with an increased risk of death after AHCT. To our knowledge this is the first time that a gender-specific effect on survival after AHCT for MM has been observed. However, the finding is compatible with the shorter survival in male myeloma patients reported in a population-based study from Sweden that included transplanted and nontransplanted patients.30 Our findings therefore highlight the need to investigate if gender disparity in outcomes of MM treatment is related to disease characteristics, treatment regimens or gender-specific comorbidities.
Registry studies are characterised by a number of benefits and limitations.40 Key limitations of this study include the lack of prognostic markers and details regarding treatment before or after AHCT, including maintenance treatments. However, a skewed representation of prognostic factors is unlikely given the large number of patients included. Furthermore, the study included only patients who underwent AHCT. The findings therefore only apply to a selected population and cannot address a comparison of AHCT with nontransplant treatments. It is worth noting that selection of MM patients for AHCT is not limited to older patients. A Dutch population-based study showed that only 36% of patients aged ⩽65 years who were diagnosed with MM in 2001–2005 underwent AHCT.32 In a recent study by the Mayo clinic, 56% of patients aged ⩽65 years who were diagnosed with MM in 2001–2010 underwent AHCT, compared with 21% of patients aged >65 years.41 It is an important strength of this investigation that it included an unprecedentedly large number of MM patients, thereby allowing statistically well-powered subgroup analyses. Furthermore, transplants were performed at almost 500 centres in 31 nations. Thus, the study provides a representative and realistic view of the trends in both utilisation and outcome of AHCT for MM in Europe, particularly with regards to patient age. The results demonstrate for the first time that the number of patients who undergo AHCT for the treatment of MM across Europe increased substantially in recent years. The data also show a substantial increase in the proportion of older patients amongst those who are selected for AHCT, and demonstrate that AHCT has become safe for selected patients of all age groups. Moreover, the findings demonstrate that post-transplant survival has improved more in older than in younger patients. Although the results from this study do not allow the conclusion that AHCT itself has improved the outcome of MM patients, they demonstrate that outcomes have improved for patients who are selected for AHCT, and have improved more for older than younger patients. It is likely that this improvement has resulted from the combined effects of novel therapies and AHCT. Further studies now need to investigate the optimal selection of patients at different ages for, and timing of, AHCT in the context of novel therapies.
Kyle RA, Rajkumar SV . Epidemiology of the plasma-cell disorders. Best Pract Res Clin Haematol 2007; 20: 637–664.
Parkin DM, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74–108.
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC . Multiple myeloma. Lancet 2009; 374: 324–339.
Sirohi B, Powles R . Epidemiology and outcomes research for MGUS, myeloma and amyloidosis. Eur J Cancer 2006; 42: 1671–1683.
McElwain TJ, Powles RL . High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983; 2: 822–824.
Gore ME, Selby PJ, Viner C, Clark PI, Meldrum M, Millar B et al. Intensive treatment of multiple myeloma and criteria for complete remission. Lancet 1989; 2: 879–882.
Jagannath S, Barlogie B, Dicke K, Alexanian R, Zagars G, Cheson B et al. Autologous bone marrow transplantation in multiple myeloma: identification of prognostic factors. Blood 1990; 76: 1860–1866.
Barlogie B, Alexanian R, Dicke KA, Zagars G, Spitzer G, Jagannath S et al. High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood 1987; 70: 869–872.
Barlogie B, Hall R, Zander A, Dicke K, Alexanian R . High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood 1986; 67: 1298–1301.
Fermand JP, Levy Y, Gerota J, Benbunan M, Cosset JM, Castaigne S et al. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft. Blood 1989; 73: 20–23.
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.
Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.
Ozaki S, Harada T, Saitoh T, Shimazaki C, Itagaki M, Asaoku H et al. Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the japanese society of myeloma and the european myeloma network. Acta Haematol 2014; 132: 211–219.
Jantunen E, Kuittinen T, Penttila K, Lehtonen P, Mahlamaki E, Nousiainen T . High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (>or=65 years) myeloma patients: comparison with younger patients treated on the same protocol. Bone Marrow Transplant 2006; 37: 917–922.
Kumar SK, Dingli D, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: Results from a matched pair analysis. Am J Hematol 2008; 83: 614–617.
Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F et al. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood 2013; 122: 1376–1383.
Qazilbash MH, Saliba RM, Hosing C, Mendoza F, Qureshi SR, Weber DM et al. Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma. Bone Marrow Transplant 2007; 39: 279–283.
Bashir Q, Shah N, Parmar S, Wei W, Rondon G, Weber DM et al. Feasibility of autologous hematopoietic stem cell transplant in patients aged >/=70 years with multiple myeloma. Leuk Lymphoma 2012; 53: 118–122.
Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 2001; 114: 600–607.
Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood 2004; 104: 3052–3057.
Merz M, Neben K, Raab MS, Sauer S, Egerer G, Hundemer M et al. Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents. Ann Oncol 2014; 25: 189–195.
Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S, Leung N et al. Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 2007; 39: 605–611.
Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370: 1209–1218.
Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E . Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood 2010; 115: 3655–3663
Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL et al. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 2009; 23: 1904–1912.
Moreau P, Avet-Loiseau H, Harousseau JL, Attal M . Current trends in autologous stem-cell transplantation for myeloma in the era of novel therapies. J Clin Oncol 2011; 29: 1898–1906.
Palumbo A, Sezer O, Kyle R, Miguel JS, Orlowski RZ, Moreau P et al. International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia 2009; 23: 1716–1730.
Brenner H, Gondos A, Pulte D . Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111: 2521–2526.
Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516–2520.
Turesson I, Velez R, Kristinsson SY, Landgren O . Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol 2010; 28: 830–834.
Pulte D, Gondos A, Brenner H . Improvement in survival of older adults with multiple myeloma: results of an updated period analysis of SEER data. Oncologist 2011; 16: 1600–1603.
Schaapveld M, Visser O, Siesling S, Schaar CG, Zweegman S, Vellenga E . Improved survival among younger but not among older patients with multiple myeloma in the Netherlands, a population-based study since 1989. Eur J Cancer 2010; 46: 160–169.
Pozzi S, Marcheselli L, Bari A, Liardo EV, Marcheselli R, Luminari S et al. Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br J Haematol 2013; 163: 40–46.
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 2014; 28: 1122–1128.
Crawley C, Iacobelli S, Bjorkstrand B, Apperley JF, Niederwieser D, Gahrton G . Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007; 109: 3588–3594.
Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.
Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.
McCarthy PL Jr, Hahn T, Hassebroek A, Bredeson C, Gajewski J, Hale G et al. Trends in use of and survival after autologous hematopoietic cell transplantation in North America, 1995-2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age. Biol Blood Marrow Transplant 2013; 19: 1116–1123.
Costa LJ, Zhang MJ, Zhong X, Dispenzieri A, Lonial S, Krishnan A et al. Trends in utilization and outcomes of autologous transplantation as early therapy for multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 1615–1624.
Levine MN, Julian JA . Registries that show efficacy: good, but not good enough. J Clin Oncol 2008; 26: 5316–5319.
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 2013; 28: 1122–1128.
HG has been a consultant for Janssen, Celgene, Novartis, Onyx and Millennium, has received honoraria from Janssen, Celgene, Novartis, Onyx, Chugai and Millennium, and has received research funding from Janssen, Celgene, Novartis and Chugai. GM has received remuneration from Janssen and Celgene. PM has been a consultant for and received honoraria from Celgene, Janssen, and Millenium. SS has received honoraria from Celgene and Janssen and research funding from Celgene. PS has received honoraria and research funding from Celgene, Janssen and Onyx. The remaining authors declare no conflict of interest.
HWA designed the research, analysed and interpreted the data and wrote the manuscript. RS analysed the data and commented on the manuscript. JH analysed the data. SS, LG, and NK commented on the research design, interpreted the data, provided patients and commented on the manuscript. HG, AMS, GJM, PM, MA, GM, NR, MB, GC and PS interpreted the data, provided patients and commented on the manuscript.
About this article
Melphalan dose in myeloma patients ≥65 years of age undergoing high-dose therapy and autologous stem cell transplantation: a multicentric observational registry study
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