|Year : 2022 | Volume
| Issue : 2 | Page : 125-130
Evaluation of the clinico-laboratory manifestations of newly diagnosed multiple myeloma
Angela Ogechukwu Ugwu
Department of Haematology and Immunology, College of Medicine, University of Nigeria, Nsukka, Ituku/Ozalla Campus, Enugu, Nigeria
|Date of Submission||05-Nov-2021|
|Date of Decision||22-Nov-2021|
|Date of Acceptance||17-Dec-2021|
|Date of Web Publication||3-Mar-2022|
Angela Ogechukwu Ugwu
Department of Haematology and Immunology, College of Medicine, University of Nigeria, Nsukka, Ituku/Ozalla Campus, Ituku-Ozalla, Enugu, PMB 01129.
Source of Support: None, Conflict of Interest: None
Background: Multiple myeloma (MM) is a very common hematological malignancy and constitutes about 10% of hematological malignancies. Laboratory investigations including haematological, biochemical, and molecular studies play an important role in the diagnosis, monitoring of response, and relapse in patients with MM. Objectives: The objectives of this article were to assess the initial clinical features, hematological profile, and biochemical parameters of newly diagnosed patients with MM. Materials and Methods: This was a retrospective study of MM patients seen from February 2010 to January 2020 at a tertiary hospital in Nigeria. A total of 51 patients’ case notes were retrieved from the Medical Records Department of the hospital. The socio-demographic data were collected using a Microsoft Excel Sheet. Data on age, sex, hematological parameters, presence of bone lesions (fractures, and osteolytic findings from radiographs), and biochemical parameters were extracted and analyzed. Results: The median age was 60.5 years, and the mean age was 59.6 ± 9.3 with a range of 35–89 years and a male-to-female ratio of 1.7:1. Only 1 (2.0%) patient was aged below 40 years, and the rest 50 (98.0%) were above 40 years of age. The 61–70 age group had the highest number of cases, 31 (60.8%). The mean hemoglobin, white cell count, and platelet count were 7.96 ± 2.2; 6.76 ± 0.6; and 213.50 ± 98 respectively. Serum protein was >80 g/L in 33 (64.7%) and <80 g/L in 18 (35.3%) patients. Two-thirds of the patients, 34 (66.7%) had albumin level <35 g/L. The mean albumin and globulin levels were 36.2 ± 10.9 and 59.2 ± 1.9 respectively, giving an albumin–globulin ratio (AGR) of 0.611. The mean calcium level was 2.6 ± 0.29 mmol/L. The overall mean urea and creatinine levels were 8.02 ± 3.2 (mmol/L) and 169.5 ± 89.4 (μmol/L), respectively. The most common clinical presentations were weakness, pallor, and bone pains with a proportion of 49 (96.1%), 47 (92.2%), and 45 (88.3%), respectively. Conclusion: The physicians should be alerted on the possibility of MM when an elderly patient presents with weakness and bone pains. The AGR is commonly low, connoting a poor prognosis.
Keywords: Anemia, biochemical profile, hematological parameters, lytic lesion, plasma cell, renal failure
|How to cite this article:|
Ugwu AO. Evaluation of the clinico-laboratory manifestations of newly diagnosed multiple myeloma. Int J Med Health Dev 2022;27:125-30
| Introduction|| |
Multiple myeloma (MM) is a malignancy of the plasma cells which is prevalent worldwide with considerable morbidity and mortality. There is a clonal proliferation of the abnormal B-cell leading to overproduction of M-proteins, which deposit in multiple organs leading to end-organ destruction. MM may clinically present as bone pains, anemia, with features of osteolytic bone lesions, immune paresis, clonal gammopathy, hyperviscosity, and nephropathy. Neoplastic plasma cells home to the bone marrow proliferate and displace normal cells. This results in disease onset and symptom manifestation such as anemia and bone pain.
The etiology of MM is not known however; there are known or associated risk factors including exposure to radiation, use of organic chemicals, and petrochemicals. Several mutations have been discovered to have a high frequency in MM such as those seen in KRAS, NRAS, TP53, and FAM46C. Despite the discovery of these mutations, no conclusive evidence shows that they are direct cause of MM or its disease progression.
MM is classified as secretory—with production of immunoglobulin G in 75% of cases and immunoglobulin A in 25% of cases—or non-secretory where no immunoglobulins are found either in serum or urine. The non-secretory MM is very rare and is seen in about 3% of cases of MM.
Epidemiologically, MM is seen mainly in the elderly population and rarely among those who are 40 years and below. Its prevalence is twice higher in Blacks than in the White population with a male preponderance.,,,,
Laboratory testing is paramount in the diagnosis and management of MM.
The basic investigations for the diagnosis and staging of MM include full blood count, bone marrow aspiration and biopsy, biochemical tests including serum and urine protein electrophoresis, serum calcium, albumin globulin ratio (AGR), and radiographic skeletal survey. These investigations are readily available in developing countries of the world, and thus the diagnosis of MM can easily be made.
The International Myeloma Working Group (IMWG) made recommendations in their guidelines for the use of several biochemical tests for the diagnosis, monitoring, and management of the disease, including immunofixation electrophoresis, serum-free light chain assay, cytogenetics, fluorescent in-situ hybridization (FISH), magnetic resonance imaging, and fluorodeoxyglucose (FDG)-positron emission tomography (PET). These tests are performed on minimally invasive specimens and can collectively identify the vast majority of myeloma cases in most high-income countries. A diagnosis usually relies on the presence of at least 10% of the bone marrow-nucleated cells being plasma cells.
MM is an incurable disease with a progressively increasing overall survival due to availability of novel and targeted therapies. [1,5] The treatment protocol includes use of immunomodulatory agents, steroids, proteasome inhibitors, and autologous stem cell transplantation. The choice of therapy largely depends on patient’s age and performance status. The 5-year survival rate in MM is 50% in high-income countries,,,, but lower in low-income countries like Nigeria with 7.6–15.5% year survival.,
The aim of this paper was to describe the clinical and laboratory manifestations of newly diagnosed MM patients in University of Nigeria Teaching Hospital, Ituku-Ozalla Enugu, Nigeria. It provided an up-to-date clinicolaboratory profile of patients with newly diagnosed MM in order to improve high index of suspicion among clinicians.
| Materials and Methods|| |
All patients diagnosed with MM presented at the clinic from February 2010 to February 2020.
This is a retrospective study of 51 patients, whose case notes were retrieved from the Medical Records Department.
Data collection tool
The socio-demographic data were collected using a Microsoft Excel. Data on the age, sex, hematological parameters (full blood count and erythrocyte sedimentation rate), presence of bone lesions (fractures, osteolytic findings from radiographs), and biochemical parameters (serum protein, urea, and creatinine) were extracted and analyzed. Renal impairment was defined as creatinine level of ≥173 µmol/L.
Analysis of the data was done using the Statistical Package for Social Sciences (SPSS) version 21 (IBM, Chicago, IL, USA). Descriptive analyses of frequencies were done for all variables. Relationships between the variables where applicable were expressed using odd ratios (ORs) and 95% confidence intervals. A P-value less than 0.05 was considered statistically significant.
Ethical clearance for this study was obtained from the University of Nigeria Teaching Hospital Research Ethics Committee.
| Results|| |
A total of 51 patients were studied within this period. The median age was 60.5 years and the mean age was 59.6 ± 9.3 with a range of 35–89 years and a male-to-female ratio of 1.7:1. Only 1 (2.0%) patient was aged below 40 years, and the rest (50/51, 98.0%) were above 40 years of age. The 61–70 age group had the highest number of cases [21 (41.2%)] [Table 1].
The mean hemoglobin, white cell count, and platelet count were 7.96 ± 2.2, 6.76 ± 0.6, and 213.50 ± 98, respectively. Majority of the patients [45 (88.2%)] had hemoglobin level less than 10 g/dL at presentation. Six patients (11.8%) had a hemoglobin level >10 g/dL, whereas 17 patients (33.3%) had a hemoglobin level below 8 g/dL and the rest 28 (54.9%) had a hemoglobin level between 8 and 10 g/dL. A platelet count above 100 × 109/L was seen in 47 patients (92.2%). Only 3 patients (5.9%) had a WBC count less than 2 × 109/L, whereas 48 (94.1%) had a WBC count ranging between 2.5 × 109/L and 12.5 × 109/L. Only 5/51 (9.8%) patients had ESR below 100 mm/1st hour. The rest [46/51 (90.2%)] had ESR more than 100 mm/1st hour with majority [40/51 (78.4%)] having >150 mm/1st hour. Bone marrow plasmacytosis was evident in all the patients. More than half of the patients 28/51 (55%) had a plasmacytosis of 10% to 30%. Further details were represented in [Figure 1].
The mean values of the hematological parameters were as shown in [Table 2]. Serum protein was >80 g/L in 33 (64.7%) and <80 g/L in 18 patients (35.3%). Two-thirds of the patients [34 (66.7%)] had albumin level <35 g/L. The mean albumin and globulin levels were 36.2 (10.9) and 59.2 (1.9) respectively, giving an AGR of 0.611. Only 19 (37.3%) patients had beta 2-microglobulin result documented. Thirteen (68.4%) had beta 2-microglobulin levels above 5.5 mg/L.
Only 6 (11.8%) patients had a calcium level >2.75 mmol/L. The mean calcium level was 2.6 ± 0.29 μmol/L. The overall mean urea and creatinine levels were noted to be 8.02 ± 3.2 (μmol/L) and 169.5 ± 89.4 (μmol/L), respectively. A quarter of the patients (25.5%) had a creatinine level of >173 µmol/L. Bence Jones Protein was negative in 25 (49.0%) patients and positive in 26 (51.0%) patients. Seven (8.0%) patients had no record of the Bence Jones protein test result.
The commonest clinical presentations were weakness, pallor, and bone pains with a proportion of 49 (96.1%), 47 (92.2%), and 45 (88.3%), respectively. None of the patients had hepatomegaly or splenomegaly. Further details on clinical presenting features were shown in [Table 3].
Radiography of the spine, chest, lower, and upper extremities showed that 41 (80.4%) had evidence of one or more lytic lesions, whereas those who presented with pathological fractures were only 23 (45.1%).
| Discussion|| |
MM is a hematological malignancy seen in elderly and the middle-aged population. It was observed in this study that 2% of myeloma cases were below 40 years of age. This is comparable with Kyle et al., who found that the prevalence of MM among those below 40 years to be 3%. Chowdhury and Sultan et al. however, found a higher prevalence of 15.63% and 13.1%, respectively. The higher prevalence found among those aged below 40 years could have been because of the patient population included in the study. From this study, the mean age was 59.6 years which is comparable to 58.8 years documented by Kaur et al. and Odunukwe et al. However, a median age of 60.5 years was found in this study and is similar to findings from other studies with median ages of 61, 62.5, and 62 years by Eren et al., Nwabuko et al., and Madu et al. Hussain et al. with a mean age of 61.8 showed a higher female prevalence. This study showed a higher male prevalence of MM which is similar to other findings.,
In this study, the commonest clinical presentation was weakness in over 90% of cases. Chowdhury and Kyle et al. presented 87.5% and 32%, respectively. Extra medullary involvement is not so common in MM at initial diagnosis. It often occurs following relapse with disease progression and is associated with a poorer outcome of the disease., Involvement of the liver and spleen may require investigations to rule out other plasma cell dyscrasias including amyloidosis. None of the patients was found to have hepatosplenomegaly.
There is bone involvement which is a result of myeloma cells directly stimulating osteoclast formation by releasing a variety of proinflammatory osteoclast-activating factors (OAFs), such as receptor activator of nuclear factor κB (NF-κB) ligand (RANKL), tumor necrosis factor α (TNF-α), and other cytokines. Most patients presented with bone pains (88.3%) in this study. This is comparable to 80.3% by Sultan et al., 78.1% by Madu et al., and 70% by Hiasa et al. Additionally, pathological factures were noted in 45.1%. Odunukwe et al. pathological factures were noted 44.3%, whereas Madu et al. noted 69%.
Other physical findings include palor 92.2% and fever which was seen in 29.4% of the patients. Similar findings of palor and fever by Chowdhury were 90.63% and 31.25%. There was no hepatomegaly or splenomegaly seen in all the cases reviewed. The increased number of patients with deranged haematological and biochemical parameters observed in this study may have been because the patients presented at the late stages of the disease and hence had more end organ damage.
Laboratory findings showed that most of our patients presented with anemia (88.2%). This is consistent with 84.45% and 85.3% noted by Liu et al. and Birgegård et al., but higher than the values noted by Kaur et al. and Chowdhury. Anemia is very common in patients with MM. This results from infiltration of the marrow by neoplastic plasma cell which crowd out the normal marrow cells. Also renal impairment leads to reduction in the production of erythropoietin which results in decreased erythropoiesis. All these could explain the anemia seen in patients with MM.
Thrombocytopenia and leukopenia were not observed in 92.2% and 94.1%, respectively. The reason may be because thrombocytopenia and leukopenia are not commonly seen at the initial stages unlike anemia. Thrombocytopenia and leukopenia are often seen on commencement of chemotherapy in MM.,
As a result of the increased paraprotein levels in MM, the erythrocyte sedimentation rate is usually very high. In this study, 90.2% had an ESR >100 mm/1st hour. This is comparable to previous findings. Hussain et al. noted that 65.3% of the cases had elevated ESR, whereas only 27% had values >100 mm/1 h. Diwan et al. reported that 100% of cases studied had ESR >100 mm/1st hour. The difference in ESR may be due to variation in the stages of MM at presentation. ESR has been shown to be significantly higher in MM patients in stage 3 disease than those in stage 1 disease.
The biochemical profiles were also analyzed and in this study a serum creatinine level of >173 µmol/L was found in 25% of the cases. This is similar to Kyle et al. and Chowdhury who found 19% and 21.87%, respectively. Serum calcium was elevated in 11.8%. This is comparable to 16.8% found by Bao et al., whereas positive Bence Jones was noted in 51% which is higher than the value obtained by Madu et al. and Ramani et al. Differences in genetic background, culture, climate, and lifestyle patterns might all contribute to disparities across regions.,
Ubiquitous tumor-induced bone destruction and resorption often led to efflux of calcium into the extracellular space. Furthermore, hypercalcemia is often a consequence of decreased glomerular filtration rate resulting from impaired renal function.
The two other biochemical parameters important as markers of tumor burden are albumin level and beta-2 microglobulin. The beta-2 microglobulin was done in only 19 patients. The other patients were not able to run the test either due to cost or their data was missing. Those with B2 microglobulin levels of >5.5 mg/L were 68.4%. Higher levels were reported by Kaur et al., Kyle et al., and Chowdhury. The AGR was low (<1.3) which underscores a poor prognosis for the patients. This has shown that most of the patients presented at advanced stages of the disease. Higher values of AGR was associated with better overall survival rate. Albumin and globulin had remarkable value in the prognosis of cancers since they are closely associated with the nutritional status and the immunity. Bi et al. reported that a low AGR <1.3 was associated with more adverse clinical features. Malignancies are often associated with poor nutrition and chronic the levels of albumin and globulin in the system.
One or more lytic lesions in the spine were seen using radiography in 80.4%, whereas 45.1% of the patients presented with pathological fractures. This is similar to the findings of Madu et al. and Chowdhury. Skeletal survey is routinely done for suspected cases of MM. These punched out lesions result from increased bone resorption by the osteoclasts activated by cytokines produced by the abnormal plasma cells. The radiograph of the skull and axial skeleton clearly showed these lytic lesion and fractures too. Study limitation: The major limitation of this study was in its retrospective design with some missing data.
| Conclusion|| |
MM occur commonly in elderly and the AGR is usually low—connoting a poor prognosis. Diagnosing MM at an early stage and early presentation of patients, will definitely prevent the complications which include pathological fractures, lytic bone lesions, renal impairment, and moderate-to-severe anemia that these patients presented with. A high index of suspicion is needed for the physicians managing elderly patients who presented with weakness and bone pains.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]