|Year : 2015 | Volume
| Issue : 2 | Page : 58-63
Multiple myeloma: The burden and clinico-laboratory characteristics in a Nigerian foremost tertiary hospital
John Ayodele Olaniyi, Florence Olamide Fowodu
Department of Haematology, College of Medicine, University College Hospital, PMB 5116, Ibadan, Nigeria
|Date of Web Publication||7-Jul-2015|
John Ayodele Olaniyi
Department of Haematology, College of Medicine, University College Hospital, PMB 5116, Ibadan
Source of Support: None, Conflict of Interest: None
Objectives: To determine the burden, the clinical and laboratory pattern of presentation of multiple myeloma (MM) in Ibadan, South-Western Nigeria. Materials and Methods: A retrospective study of cases of MM from December 2007 to November 2012. Results: Records of 21 cases of MM were retrievable. The median age was 60 years, with age range of 40-95 years. The M:F ratio was 1.1:1. IgG MM was the most common, found in 14 (70%). Most cases were referred from other clinical departments of the University College of Hospital with Orthopaedics department referring the highest number (33.3%). The most common complaint included low back and waist pain in 20 (96%) of which 9 (44%) had difficulty in walking but 4 (19%) actually had demonstrable paraparesis. Two cases (9.6%) presented in unconscious state while a case (4.3%) respectively presented with malignant pleural effusion, sacral plasmacytoma and cauda-equina syndrome. The mean hematocrit, white cell count and platelet count were 26.5%, 6, 216/mm 3 and 264, 778/mm 3 respectively. Biochemical abnormalities included hyperuricemia (>6 mg/dl) in 4/15 (26.6%). Uremia (urea 50-200 mg/dl) was found in 4/21 (19%), hypocalcemia (Ca ++ <9 mg/dl) in 6 (35.3%). Paraproteinurial in 9 (42.9%). Elevated erythrocyte sedimentation rate (>100 mm/H) values were recorded in 19 (90.5%). Main Radiological features were osteolytic lesions and osteoporosis in 18 (85.7%). Serum protein electrophoretic pattern showed abnormally thick gamma band in 47.1%, thick beta band in 19.1%, marked polyclonal gammopathy in 1 (4.8%) and 4 (18.4%) had nonsecretory MM. Bone marrow studies showed presence of abnormal plasmacytosis in all ranging from 20% to 80% infiltration. Therapy was mainly by combination of melphalan, prednisolone and thalidomide (M + P + T). Those who had thalidomide appear to have better survival. Conclusion: MM is a heterogeneous disease with diverse clinical and laboratory features. An average of 4 cases presented per year; bony presentations predominate, IgG MM was the commonest and hypercalcemia was not documented.
Keywords: Disease burden, 5 years review, Ibadan (Nigeria), multiple myeloma, presentation pattern
|How to cite this article:|
Olaniyi JA, Fowodu FO. Multiple myeloma: The burden and clinico-laboratory characteristics in a Nigerian foremost tertiary hospital. J Appl Hematol 2015;6:58-63
|How to cite this URL:|
Olaniyi JA, Fowodu FO. Multiple myeloma: The burden and clinico-laboratory characteristics in a Nigerian foremost tertiary hospital. J Appl Hematol [serial online] 2015 [cited 2018 Dec 19];6:58-63. Available from: http://www.jahjournal.org/text.asp?2015/6/2/58/160200
| Introduction|| |
Multiple myeloma (MM), first described in 1948, is a debilitating plasma cell malignancy.  It represents part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance, which is asymptomatic, to plasma cell leukemia which represents very advanced disease.
Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, along with elaboration of monoclonal protein in the blood and/or urine, and associated organ dysfunction.  It accounts for approximately 1% of neoplastic diseases and 13% of hematologic cancers. In Western countries, the annual age adjusted incidence is 5.6 cases per 100,000 persons  and median age at diagnosis is approximately 70 years; only 37% of patients are younger than 65 years, 26% are between the ages of 65 and 74 years, and 37% are 75 years of age or older. 
As illustrated in [Figure 1], it is characterized by a clonal proliferation of malignant plasma cells with excessive production of monoclonal paraproteins (M-protein). The malignant plasma cells interfere with hemopoiesis resulting in progressive bone marrow failure reflecting as anemia, leukopenia and thrombocytopenia. The malignant cells accumulate in the marrow and may result in lytic boney lesions and/or causing bone pain, hypercalcemia, spinal cord compression and renal failure.  Monoclonal paraproteins elaborated by the malignant cells are accountable for hyperviscosity, amyloidosis, as well as renal failure and impaired humoral immunity.
|Figure 1: Pathophysiology of disease manifestations of multiple myeloma (culled from: http://accessmedicine.com)|
Click here to view
The clinical features of MM usually include bone pains involving principally the bones of the axial skeleton. Since bone pain is common at the age group involved and because there are numerous causes of bone pain, patients tend to self-medicate, seek advice and treatment at various private facilities where the index of suspicion tend to be low. Definitive diagnosis of MM tends to be made at the teaching hospitals where the index of suspicion is relatively higher and facilities available for detailed investigation.
The diagnosis of MM can be suspected through a full blood count (FBC) where isolated anemia could be the major finding, but at times there could be accompanying leukopenia and thrombocytopenia. Presence of roulaux formation of red cells on peripheral blood film review heightens the suspicion of MM.
Raised calcium, renal failure, anemia, along with radiological features of bone lesions are now the accepted diagnostic criteria of MM. ,
Skeletal survey using X-rays may reveal presence of oesteolytic lesions and at times osteoporosis but magnetic resonance imaging (MRI) and computerized tomography/position emission tomography are far more sensitive and provide superior information to X-rays but the cost is prohibitive to most patients and the equipment cannot be readily assessed in most facilities.
Other useful diagnostic and mandatory investigations in MM includes bone marrow aspiration (BMA), which is the preclusive exercise of the hematologists. This often reveals presence of abnormal/malignant plasma cells in the bone marrow, and this should be equal to or more than 10% to satisfy the diagnostic criteria. 
In recent years, the introduction of autologous stem-cell transplantation and the availability of agents such as thalidomide, lenalidomide, and bortezomib have changed the management of myeloma and extended overall survival. , In patients presenting at an age under 60 years, 10-year survival is approximately 30%. 
In order to enhance prompt, accurate and early diagnosis of MM, this study documents the burden and the pattern of clinical, as well as laboratory presentation of MM patients to the University College of Hospital (UCH), Ibadan.
| Materials and methods|| |
This is a retrospective study carried out in the Department of Haematology, UCH, Ibadan, Nigeria. Cases of MM seen in the Department from December 2007 to November 2012 were collated and analyzed.
The case notes, along with departmental pink folders of each of the patients over the stipulated period were retrieved and analyzed for age, sex, source of referral, mode of presentation, nature of complaints, documented physical signs and relevant laboratory investigations like hematological profiles and biochemical profiles, that is, liver function tests, electrolytes and urea, uric acid plus creatinine, pattern of serum protein electrophoresis (SPE) and bence jones protein (BJP). Also, radiological findings, as well as treatment modalities were noted.
The 21 MM patients were diagnosed following referral through detailed medical history and physical examination, routine laboratory testing (complete blood count, chemical analysis, serum and urine protein electrophoresis with immunofixation, and quantification of monoclonal protein), and bone marrow examination but we were unable to subject the marrow aspirate to cytogenetic analysis or fluorescence in situ hybridization (FISH). They also had conventional radiography, skeletal survey, of the spine, skull, chest, pelvis, humeri, and femoral. These remain the standard to identify myeloma-related bone lesions. None of the patients could afford MRI which is recommended to evaluate symptoms in patients with normal results on conventional radiography.
The ranges, mean, median, and proportions in percentages were determined using excel package.
| Results|| |
Over the 5-year period, records of 21 MM cases were retrievable. This represents an average of 4.2 cases per year. The age range was 40-95 years with a median age of 60 years. The M:F ratio was 1.1:1. Refer to [Figure 2]. According to [Figure 1] and 15 (71.4%) were <65 years of age while 6 (28.6%) were older than 65 years.
According to [Table 1], most cases were referred to hematology department from within the UCH clinical departments. Highest proportion of 33.3% was referred from Orthopaedics Department followed by renal unit (23.8%) and (13.8%) presented directly to Haematology Department. Others are as shown in [Table 1].
The most common complaint was low back/waist/hip pain with or without tenderness in 96% and 44% had associated difficulty with walking. Other presenting complaints include chest pain, features of symptomatic anemia in 3 (14.3%), epigastric pain in 2 (9.5%), physical findings included tenderness of the pelvic bones with paraparesis in 8 (38.1%) while a case each (4.8%) presented with malignant pleural effusion, sacral plasmacytoma and caudaequinal syndrome respectively.
Central Nervous System Features
Hearing loss in 1 (4.8%), demonstrable paraparesis in 4 (19%), unconsciousness in 2 (9.5%) and irrational talk in 1 (4.8%).
Provisional Diagnosis Prior to Referral
Nine (42.9%) of the patients were already provisionally assigned a diagnosis. Tuberculosis spine in 3 (13.8%), lumbago (back pain) in 2 (9.6%), cauda-equina syndrome in 1 (4.8%), maltoma in 1 (4.8%) and myelopathy in 2 (9.6%). Appropriate treatment according to such diagnosis was already commenced before referral.
Myeloma by Immunoglobulin Types
Records of immunoglobulin electrophoresis and quantitation were found in 20 MM patients; Out of the 20, eletrophoretic pattern was found to be normal (nonsecretory) in 4 (20%), IgG MM constituted 14 (70%), IgE and IgA accounted for 1 (5%) each.
Full blood count result revealed a mean hematocrit, white cell count and a platelet count of 26.5% (range 15-38), 6,216/mm 3 and 264,778/mm 3 respectively. Therefore, anemia appears to be a constant feature of MM in this study. Erythrocyte sedimentation rate (ESR) ranges between 15 mm and 150 mm in the 1 st h with 19 (90.5%) having elevated values of ESR >100 mm in 1 st h.
Records of uric acid were obtained in 15/21 patients. Out of the 15, uric acid level was within normal range in 11 (73.3%) while 4 (26.7%) had elevated level (ranging between 6 mg/dl and 12 mg/dl). Normal urea was recorded for 17 (81%), while 4 (18%) had elevated urea (urea > 50 mg/dl) with majority having urea levels within the range of 100-200 mg/dl. Hypocalcaemia (Ca ++ ˂9 mg/dl) was found in 6 (28.6%) and 15 (71.4%) had normal (9-11 mg/dl) calcium level. Urinary paraprotein level (by heat and immunofixation method) was positive only in 9 (42.9%), negative in 8 (38.1%) and inconclusive in the rest.
Serum Protein Electrophoresis
Serum protein electrophoretic pattern retrieved for 19 patients showed thick gamma band in 6 (47.1%), thick beta band in 3 (19.1%), beta-gamma fusion in 2 (9-6), faint gamma in 2 (9-6%), polyclonal gammopathy in 1 (4.8%), late gamma in 1 (4.6%) and 4 (16%) had nonsecretory MM.
Bone Marrow Aspiration Study
The presence of abnormal plasmacytosis ranging from 20% to 80% was documented in all the 21 MM patients.
Out of the 21 MM patients, fractures were not determined in 4 while various forms of fracture were determined in 17 (81%). Out of the 17 MM patients with demonstrable fractures, vertebrae collapse at various levels was found in 6 (28.6%), femoral fractures in 4 (23.5%), humeral fractures in 4 (23.5%) and scapular/claviclar fracture in 3 (14.3%). Furthermore, osteolytic or osteoporosis was demonstrated in 18 (85.7%) of the cases.
Seven (28%) were treated with combination of melphalan, prednisolone (M + P) and thalidomide (M + P + T) while 5 (23.8%) had combination therapy of vincristine, adriamycin and dexamethazone and 9 (42.9%) cases had M + P as therapy. Those who had thalidomide appear to have roughly better quality of life since 2 of them are still alive as at the time of writing this report.
| Discussion|| |
Multiple myeloma is an age long hematological malignancy that progresses insidiously but becomes invariably fatal. Previous studies established that it is more common in blacks than in the Caucasians. , The median survival was reported to be 3 years.  This index study revealed an average of 4.2 MM cases per year. These 21 MM patients presented with various complications like progressive bone marrow failure, osteolytic lesions of bones, abnormal production of monoclonal proteins which eventually cause hyperviscosity, renal failure and many other organ dysfunctions; significant proportion presented with biochemical derangements like hyperuricemia and hypo-albuminemia. Some of these patients presented with combinations of these pathological entities hence making a high index of suspicion a key to diagnosis.
In this study, a median age of 60 years is quite similar to the findings in other studies within the country. In Enugu, Nigeria, Madu et al.;  documented a median age of 62 years while Salawu et al. of Obafemi Awolowo University Ile-Ife  also documented a similar median age of 60 years. However, a median age of 64 years was obtained by Omoti and Omuemu of the University of Benin.  The male:female ratio in this study is 1.1:1, which aligns with the findings of previous workers. ,,,, However, a study in Nigeria documented a male:female ratio of 4.4:1 
Like in many other studies, ,, the dominating clinical complaints consist of bone pains with up to 96% of our MM patients presenting with the complaints of low back and waist pain. This explains why the orthopedic department of the hospital, where the index of suspicion is relatively high, happened to be the major source of referral of MM patients to the Department of Hematology.
The pattern of presentation of MM to the UCH, Ibadan clearly depicts late presentation with the majority of them presenting with one or more complications of the disease. As stated in the result, some MM patients presented in unconscious states, which may not be unconnected with hyperviscosity states while some were paraplegic at presentation due to lumbar vertebrae affectation as demonstrated by radiological studies. However, bony complications appear to be the commonest with 81% of the MM patients having various types of pathological fractures, that is, vertebrae collapse at various levels in 6/17 (28.6%), femoral fractures in 4/17 (23.5%), humeral fractures in 4 (23.5%) and scapular and clavicular fracture in 3/17 (14.3%). Also, osteolytic or osteoporosis was demonstrated in 1821 (85.7%) of the cases. This finding is line with the observation of other workers. ,, This also explains their presentation to the orthopedic surgeons.
Extensive laboratory investigations are required not only to diagnose MM, but also for the purpose of staging, classification and prognostication of the disease. Required studies for staging of the disease, according to the International staging system, which defines three risk groups on the basis of serum β2-microglobulin and albumin levels  and chromosomal abnormalities determination that is detected on standard cytogenetic analysis are not easily available as routine in our setting yet. Therefore, specific translocations in the immunoglobulin heavy chain region that are detected on FISH, such as t (4;14), deletion 17p13, and chromosome 1 abnormalities which are associated with a poor prognosis , cannot be easily determined and in fact most patients cannot pay out of pocket for these laboratory investigations. However, as stated in the methodology sections basic investigations suffice in managing our MM patients to a reasonable extent.
Olaniyi et al.  previously reported rare and unusual presentation of MM with pleural effusion in the facility. Other rare presentations documented in this study include sacral plasmacytoma and cauda-equinal syndrome.
Hematological investigations in this index study, that is, FBC, ESR, and BMA which are easily accessible and affordable in our setting and do strongly assist in establishing diagnosis and crudely monitors the disease affirmed anemia and elevated ESR as a constant finding in our patients. Also, BMA findings also showed significant bone marrow plasmacytosis of 20-80%.
Although previous study reported renal impairment in 20-40% with newly diagnosed disease ,, evidence of renal injury was limited to 4/15 (26.7%) with hyperuricemia while 4/15 (26.7%) had elevated urea within the range of 100-200 mg/dl. However, rather than hypercalcemia as expected, only hypocalcaemia was found in 4/21 (18%) and hypercalcemia was not documented in any of the patients. This may be attributable to failure to always calculate anion gap for the correction of calcium level. As shown in the result urinary paraprotein was positive in <50% of the patients. The outcome of SPE and quantitation showed that IgG MM was the most common, constituting 70%. This finding supports earlier documented literature, which reported in pain competency evaluation Oncology e-Rounds  that "overall, approximately 70% of patients with myeloma will have elevated IgG, 20% IgA, and 5%, 10% light chains only (BJP). About 1% will have IgD, IgE, IgM or nonsecretory disease (cancerous plasma cells that do not secrete immunoglobulin). About 30% of the time, there is an imbalance in the production of light and heavy chains resulting in excess light chains along with the monoclonal antibody."
Obviously our diagnostic ability is not strong enough to finely classify MM along prognostic classification of Durie and Salmon. We were equally unable to determine genetic alterations as well as immunophenotype our MM patients. All these, when available, shall improve the care of our MM patients and put us on the platform to participate in clinical trials on our MM patients.
Most of these patients presented late and with complications like renal failure, pathological fractures, bone marrow failures and metabolic derangement leading to a state of unconsciousness. All these, along with financial constraints, unavailability/unaffordability of modern drugs like bortezomib, lenalidomide etc., and the inability to offer bone marrow transplant to younger patients contribute to the dismal prognostic outcome of MM in Nigeria.
The data collected was not adequate for survival study. However, it was observed that those who benefited from the addition of thalidomide to melphalan and prednisolone combination chemotherapy regimen did better and in fact three of them are still alive as at the time of writing this report.
It is also observed that the index of suspicion requires upgrading especially amongst our private practitioners. The orthopedic surgeons appear to have the highest index of suspicion probably because bony complications happen to be the commonest complication of the disease in this setting. Also, many of the patients were initially ascribed a wrong diagnosis and already being treated as such before being referred.
| Conclusion|| |
Multiple myeloma is a heterogeneous disease with diverse clinical and laboratory features. It constitutes a significant burden of hematological malignancy at the institution. Orthopedic surgeons, renal physicians and gastroenterologists in particular need to exercise a higher index of suspicion for MM to minimize late presentation. By casual observation, the introduction of thalidomide in the management appears to give better response and outcome.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]