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 Table of Contents  
BRIEF REPORT
Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 149-152

Impact of delayed diagnosis of multiple myeloma


Department of Adult Hematology/Oncology, King Saud Medical City, Riyadh, Saudi Arabia

Date of Submission27-Dec-2019
Date of Decision13-Apr-2020
Date of Acceptance15-Apr-2020
Date of Web Publication16-Sep-2020

Correspondence Address:
Dr. Assem Elghazaly
Department of Adult Hematology/Oncology, King Saud Medical City, Ulisha Street, Postal Code 7790, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_90_19

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  Abstract 

BACKGROUND: Multiple myeloma (MM) is a malignant neoplasm of plasma cells. It constitutes about 1% of the entire human malignancies. The disease affects multiple body systems/organs including the kidneys, bone, hematopoiesis, and immune system. Delay in diagnosis, with a negative impact on patients' outcome particularly those with emergency presentation, had been reported. No local publication had addressed this issue. The aim of this work is to study the local practice, specifically the time from initial symptoms to the diagnosis of MM.
METHODS: This is a medical record-based study from a central hospital, Saudi Arabia. The study included all newly diagnosed patients with MM from June 2016 to January 2019.
RESULTS: A total of 22 patients were studied, of them 21 presented to our hospital emergency room with nonspecific symptoms, before the diagnosis was made for the first time. All the patients had prior visits to other clinics/centers without a definitive diagnosis reached. Back pain was the most common initial symptom. We demonstrated more frequent disease-related complications, particularly end-stage renal disease requiring hemodialysis (27%) at the time of diagnosis than that mentioned in other studies. The median time from initial symptoms to diagnosis was 204 days, which is longer than what had been shown in previous reports.
CONCLUSIONS: Delayed diagnosis of MM, with its negative impact on patients' outcome, is a challenge. In our center experience, most patients had significate disease-related complications at the time of diagnosis. Raising the awareness about red flags of back/bone pain as well as having an effective referral pathway is suggested.

Keywords: Back pain, bone pain, diagnosis, emergency room, multiple myeloma and referral


How to cite this article:
Elghazaly A, AlSwayyan A, AlGreshah H. Impact of delayed diagnosis of multiple myeloma. J Appl Hematol 2020;11:149-52

How to cite this URL:
Elghazaly A, AlSwayyan A, AlGreshah H. Impact of delayed diagnosis of multiple myeloma. J Appl Hematol [serial online] 2020 [cited 2020 Oct 22];11:149-52. Available from: https://www.jahjournal.org/text.asp?2020/11/3/149/295128


  Introduction Top


Multiple myeloma (MM) is a malignant neoplasm of plasma cells. It constitutes about 1% of the entire human and about 8%–10% of the hematological malignancies.[1],[2] The disease affects multiple body systems/organs including the kidneys, bone, hematopoiesis, and immune system. This explains the disease-related morbidity and mortality. The median age at diagnosis is 66–70 years with younger age of onset had been reported in local studies.[2],[3],[4] Recently, the international myeloma working group has published the updated diagnostic criteria of MM and other plasma cell disorders.[5] Over the last decade, there has been survival improvement. This improvement was attributed to the availability of effective therapy.[6],[7]

Delay in diagnosis had been reported, with a negative impact on the patients' outcome. Multiple factors contributed to such delay.[8],[9],[10]

The time to the diagnosis of MM has not been locally reported. This work aims at studying the local practice of MM diagnosis, specifically the time from initial symptoms to the diagnosis.


  Methods Top


This is a retrospective medical record-based study, included all newly diagnosed patients with MM in our institute (a Ministry of Health Central Hospital, KSA) between June 2016 and January 2019. The MM diagnosis is based on the International Myeloma Working Group 2014 criteria.[5] Eastern Cooperative Oncology Group criteria have been used to assess the patients' performs status.[11] The study was approved by the institutional review board.


  Results Top


The study included 22 patients, 16 males and 6 females. The median age is 70 years (range 40–100 years) with 8 (36%) patients younger than 60 years (range 40–58 years). Eleven patients were Saudi nationals. The male: female ratio was 8:3 among both citizens and other nationalities [Table 1].
Table 1: Patients' basic characteristics

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Back pain with/without other boney pain was the first presenting symptom in 19 (86%) patients. Six (27%) patients had anemic symptoms at the time of presentation. Regarding comorbidities, hypertension (HT), type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), and mental subnormality were present in 4, 2, 1, and 1 patients, respectively. Two patients had both HT and T2DM, another two with both benign prostatic hyperplasia and HT, and one patient was on treatment for acute cerebrovascular stroke, HT, T2DM, and CHD. β2 microglobulin result was not available for the majority of the patients [Table 1].

Regarding the MM-related complication, six (27%) patients were already on hemodialysis for end-stage renal disease (ESRD), with a range of 1–48 days before the diagnosis was made. Vertebral compression fracture was demonstrated in 18 (82%) patients, one of them had spinal cord compression. In addition to the vertebrae, four (18%) patients had other fracture sites: femur, humerus, sternum, and pelvis (one patient each). Pneumonia was the admission diagnosis in 3 (14%) cases [Table 2].
Table 2: Multiple myeloma-related complications at the time of diagnosis

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All the 22 patients had received symptomatic treatment in three or more other centers. Of them, 21 (95%) patients were admitted through the emergency room (ER) with nonspecific manifestations; all were diagnosed for the first time in our institute. Only one patient had been referred as a newly diagnosed MM. The median time from the initial symptoms to diagnosis is 204 days, with a range of 2–12 months.


  Discussion Top


Our study has shown a median of 204 days from initial symptoms to the diagnosis. All patients had been seen in at least three centers before the diagnosis was made for the first time. With exception of one, the entire group of patients got admitted through the ER with nonspecific symptoms. Most of the patients had disease-related complication(s) at the time of diagnosis.

The overall male:female ratio of 2.6:1 is obviously higher than the international (1.3:1) data.[2],[7],[12],[13] Interestingly, a similar high ratio among citizens had been reported in a local study.[14] The Saudi General Authority for Statistics reports male: female ratio of citizens at the age of 40–80 years as 1:1, whereas it is 3.5:1 for other nationalities of the same age group.[15] This would be one explanation for the high male: female in the current study. Having a small number of patients in the two studies, it would not be possible to draw a conclusion. The median age at diagnosis is 70 years with 36% of the patients below the age of 60 years, concordant with the international figures. However, two local different cancer centers reported younger median ages (56 and 60 years) at diagnosis.[2],[3],[4]

Back pain was the earliest and most common cause (86%) of seeking medical advice, consistent with previous studies. Regarding the disease-related complications, anemia (86%), skeletal abnormalities (81%), high serum creatinine (50%), and ESRD requiring hemodialysis at the time of diagnosis (27%); all are higher than whose were earlier reported. For example, Blimark et al. reported 49%, 77%, and 18% for anemia, skeletal abnormalities, and high creatinine, respectively, with 13% hemodialysis for ESRD in a study by Chao-Feng Cet al.[3],[4],[8],[16],[17]

The median time from initial symptoms to diagnosis is 204 days, which is obviously longer than the 99 days in a study by Friese et al.[10]

Delayed diagnosis of MM had been reported and attributed to multiple factors. First, most symptoms are vague and nonspecific. Second, the prevalence of osteoporosis and degenerative vertebral disorders in the elderly people, with associating effects and complications which resemble those of MM.[18] Third, the associating comorbidities can also steer diagnostics in a different direction. Fourth, health-care provider awareness about the disease and its manifestations. Finally, different referral routes and pathways had also shown to affect the time to diagnosis.[9],[10]

Delayed diagnosis had shown to negatively impact on the disease-free survival; however, it did not affect the overall survival. In contrary, Howell et al. had demonstrated an association between emergency presentation and advanced disease, poorer outcomes, and a worse overall survival.[8],[9],[10]

A limitation of our study is being a single-center study. The referral pathways to university hospitals and other dedicated cancer centers differ from those to central hospitals. In our study, 21 out of 22 patients were diagnosed for the first time after emergency admission for nonspecific presentation.

Several strategies had been suggested to overcome diagnostic delay. First, raising the public and the health-care providers' awareness about the red flags of back pain. New-onset back and/or other site bone pain, with certain characters, in an elderly or a middle-aged person could be a manifestation of an underlying metastasis or MM.[19] Second, educating the primary health-care/family medicine physicians about the disease-related manifestations, laboratory findings, and radiological changes. Having a clear and practical referral pathway had shown to expedite the diagnostic process.[8],[9],[10]


  Conclusions Top


Delayed diagnosis of MM, with its negative impact on patients' outcome, is a challenge. In our center experience, most patients had significate disease-related complications at the time of diagnosis. Raising the awareness about red flags of back/bone pain as well as having an effective referral pathway is suggested.

Acknowledgment

The authors would like to thank Dr Bara AlMaqadma for technical help.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.  Back to cited text no. 1
    
2.
Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol 2016;43:676-81.  Back to cited text no. 2
    
3.
Khalil SH, Padmos A, Ernst P, Clink HM. Multiple myeloma: A review of 92 cases at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Ann Saudi Med 1991;11:642-6.  Back to cited text no. 3
    
4.
Omar ZA, Abid M, Hani HA. Retrospective observational study on multiple myeloma cases admitted to Kfsh – Dammam between 1st of June 2006 till the end of December 2013. Blood 2014;124:5995.  Back to cited text no. 4
    
5.
Rajkumar VS, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15:e538-48.  Back to cited text no. 5
    
6.
Turesson I, Velez R, Kristinsson SY, Landgren O, et al. Patterns of improved survival in patients with multiple myeloma in the twenty- first century: A population-based study. J Clin Oncol 2009;28:830-4.  Back to cited text no. 6
    
7.
Blimark CH, Turesson I, Genell A, Ahlberg L, Björkstrand B, Carlson K, et al. Outcome and survival of myeloma patients diagnosed 2008-2015. Real-world data on 4904 patients from the Swedish Myeloma Registry. Haematologica 2018;103:506-13.  Back to cited text no. 7
    
8.
Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: Causes and consequences of delay in diagnosis. QJM 2007;100:635-40.  Back to cited text no. 8
    
9.
Howell D, Smith A, Appleton S, Bagguley T, Macleod U, Cook G, et al. Multiple myeloma: Routes to diagnosis, clinical characteristics and survival – Findings from a UK population-based study. Br J Haematol 2017;177:67-71.  Back to cited text no. 9
    
10.
Friese CR, Abel GA, Magazu LS, Neville BA, Richardson LC, Earle CC. Diagnostic delay and complications for older adults with multiple myeloma. Leuk Lymphoma 2009;50:392-400.  Back to cited text no. 10
    
11.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55.  Back to cited text no. 11
    
12.
Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, et al. National Cancer Institute. Availablr form: https://seer.cancer.gov/archive/csr/1975_2013. Updated September 12, 2016. [Last accessed on 2018 Dec 25].  Back to cited text no. 12
    
13.
Philip SR, Kimberly AB, William FA. Future distribution of multiple myeloma in the United States by sex, age, and race/ethnicity. Blood 2015;125:410-2.  Back to cited text no. 13
    
14.
Almueilo SH. Renal failure in patients with multiple myeloma. Saudi J Kidney Dis Transpl 2015;26:482-8.  Back to cited text no. 14
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15.
General Authority for Statistics, Kingdom of Saudi Arabia. Population Estimation. Available from: www.stats.gov.sa. [Last accessed on 2018 Dec 25].  Back to cited text no. 15
    
16.
Aya N, Nakanishi T, Azuma Y, Tsubokura Y. Impact of CRAB symptoms in survival of patients with symptomatic myeloma in novel agent era. Hematol Rep 2017;9:6887.  Back to cited text no. 16
    
17.
Chao-Feng C, Wu-Chien C, Chi-Hsiang C, Lee JC, Hsu SN. Chen JH, et al. Impact of hemodialysis on the prognosis of multiple myeloma: A nationwide populationbased study and single-institute analysis. Oncol Lett 2018;16:1991-2002.  Back to cited text no. 17
    
18.
Schentrup D. Diagnosing multiple myeloma in primary care. Clin Rev 2018 28:16-18;20-1.  Back to cited text no. 18
    
19.
Braen GR, Brown K, Deyo R, Haldeman S, et al. Acute low back problems in adults. AHCPR Publication no. 95-0642. Rockville, Md.: U.S. Dept of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1994.  Back to cited text no. 19
    



 
 
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