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ORIGINAL ARTICLE
Year : 2021 | Volume
: 46
| Issue : 3 | Page : 181-184
Diagnostic workup of multiple myeloma in resource-constrained setting: is addition of costly test to baseline profile necessary?
Richa Juneja, Haraprasad Pati, Gopila Gupta, Manoranjan Mahapatra, Seema Tyagi, Renu Saxena
Department of Hematology, All India Institute of Medical Science, New Delhi, India
Correspondence Address:
Richa Juneja
DM Fellow, Department of Hematology, All India Institute of Medical Science, New Delhi 110049
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ejh.ejh_49_20
Background Monoclonal protein detection and characterization is integral component of myeloma workup and is at times used as the first step toward diagnosis. Costs of these tests are major concern in developing countries.
Recent studies have emphasized on the prognostic importance of risk stratification with cytogenetic in patients with myeloma.
Aims We intend to analyze additional information obtained by two costly tests, namely, serum free light chain assay (sFLC) and fluorescent in situ hybridization (FISH), for high-risk cytogenetic abnormalities during baseline workup of patients with myeloma and their necessity.
Patients and methods We retrospectively analyzed laboratory data of 130 patients with myeloma enrolled at our institute between years 2016 and 2019. Subset analyses of 71 patients who underwent all three tests, namely, serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and sFLC for monoclonal protein detection, were done.
Patterns of cytogenetic abnormalities were noted in 70 patients undergoing FISH testing for high-risk cytogenetic abnormalities and serum lactate dehydrogenase (LDH) level. International staging system (ISS) and revised international staging system (RISS) categories were compared among this group of patients.
Statistical analysis used A proportion test was used.
Results SPEP detected and quantified M protein in 55 (77.4%) patients. IFE detected M protein in 68 (95.7%) patients and typing was done. sFLC ratio was abnormal in 66 (92.6%) patients. IFE and sFLC were more sensitive in detecting monoclonal protein as compared with SPEP (P=0.001 and 0.009, respectively) at diagnosis.
In 70 patients with FISH and LDH results available, seven (10%) patients had high-risk karyotype on FISH, and LDH was raised in five (7.1%). Based on these results, three (4.2%) patients who were ISS stage I were upgraded to RISS stage II and 21 (30%) ISS III patients were downgraded to RISS II category, thereby helping in 34.2% patients for accurate prognostication.
Conclusion In resource-constrained setting, using sFLC sequentially after SPEP is noninformative, but UPEP/IFE shows M band, which can be a viable approach at diagnosis. For better prognostication, FISH for high-risk karyotypic abnormalities is required.
Keywords: multiple myeloma, serum free light chain assay, fluorescent in situ hybridization
Multiple myeloma is one of the common hematological neoplasms affecting elderly [1]. This disease has seen many advances not only in treatment modalities but also in diagnostic and prognostic tools. Change in IMWG diagnostic criteria of requirement of end organ dysfunction to biomarker-based diagnosis helps in facilitating early diagnosis and treatment [2],[3]. Despite being aware of recent IMWG recommendation on workup of patients with myeloma, health care in developing world faces unique challenges [3]. Many a time what is ‘ideal’ is not affordable for majority. We intend to analyze what additional information does two costly tests, namely, serum free light chain assay (sFLC) and fluorescent in situ hybridization (FISH), add to baseline workup of patients with multiple myeloma.
Aims and objectives
The following were the aims and objectives of the study:
Evaluation of two costly tests, namely, sFLC and FISH during baseline workup of patients with myeloma.
Comparison of serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and sFLC for monoclonal protein detection.
Role of FISH in prognostication of Indian patients.
Patients and methodsWe retrospectively analyzed data of 130 patients with myeloma enrolled at our institute between years 2016 and 2019. It is a retrospective analysis of lab data and no confidential information of patient was disclosed. Hence all ethical practices were followed. Subset analyses of 71 patients who underwent all three test, namely, SPEP, IFE, and sFLC, for monoclonal protein detection were done. SPEP and IFE were done manually, and sFLC was done using free-lite assay by binding site. Relative efficiency of each of these tests in detecting monoclonal protein at baseline was compared by using proportion test.
Another subset of patients (70) underwent FISH testing on sorted plasma cells for high-risk cytogenetic abnormalities and serum lactate dehydrogenase (LDH) level. Plasma cell sorting for FISH was done by magnetic cell sorting. Testing for 13q del, t(11;14) and revised international staging system (RISS)-defined high-risk abnormalities del17p, t(4;14), and t(14;16) was performed using appropriate FISH probes. Serum albumin level, beta 2 microglobulin level, and serum LDH level at diagnosis were retracted from hospital information system. International staging system (ISS) and RISS categories were compared in this group of patients.
ResultsPatient characteristics
A total of 130 patients with myeloma were enrolled at our institute during the 3-year study period. Mean age of our study cohort was 54.4 years, with male : female ratio being 2.1 : 1. Most common clinical presentation was weakness (90.1%) followed by low backache (81.6%).
Test for monoclonal protein detection
A total of 71 patients underwent all three tests for monoclonal protein detection at diagnosis. SPEP detected and quantified M protein in 55 (77.4%) patients. IFE detected M protein in 68 (95.7%) patients and typing was done. sFLC ratio was abnormal in 66 (92.6%) patients ([Table 1]). Both IFE and sFLC were more sensitive in detecting monoclonal protein as compared with SPEP (P=0.001 and 0.009, respectively).
Table 1 Immunofixation electrophoresis and serum free light chain assay were more sensitive in detecting monoclonal protein as compared with serum protein electrophoresis (N=71)Fluorescent in situ hybridization for myeloma
For 70 patients, FISH and LDH results were available. A total of 21 (30%) patients had positive FISH results for five of the common genetic abnormalities screened. Seven (10%) patients had high-risk karyotype, and LDH was raised in five (7.1%) patients.
Of these 70 patients, 20 (28.5%) were ISS stage I, 22 (31.4%) were stage II, and 28 (40%) were ISS stage III. A total of seven (10%) patients had high-risk karyotype on FISH, and LDH was raised in five (7.1%). Overall, three (4.2%) patients who were ISS stage I were upgraded to RISS stage II. Moreover, 21 (30%) ISS III patients were shifted to RISS II category owing to absence of high-risk karyotypic abnormalities and normal serum LDH. [Table 2] shows ISS and RISS risk stratification for the study group.
Table 2 International staging system and revised international staging system categories of study cohort (N=70) Discussion SEPE and urine protein electrophoresis and serum and urine IFE and sFLC are various techniques for monoclonal protein detection [4]. Various combination of these tests have been tried, and it has been found that SPEP+IFE had comparable but less sensitivity than SPEP+sFLC in detecting monoclonal protein in patients with myeloma [5]. We found SPE alone was positive in only 77.4% patients. SPEP+IFE could detect monoclonal protein in 95.7% of patients; however, SPE+sFLC increases yield to 97.1%. Of 16 patients with no M band on SPE, 13 cases showed M band on IFE, and sFLC was abnormal in 11 cases. All except one case were light chain myeloma.
Overall, 26/66 cases had sFLC ratio more than 100 and involved light chain more than 100, that is, myeloma defining event but all had end organ damage in the form of CRAB and did not require sFLC for diagnosis. In such situation, sFLC did not provide additional information. Based on these findings, we suggest an algorithm in [Figure 1] for monoclonal protein detection in resource-constrained setting.
Figure 1 Suggested algorithm for monoclonal protein detection in patients with suspected myeloma in cost-constrained setting.Importance of FISH for high-risk cytogenetic abnormalities and LDH level in prognostication of patients with myeloma has been established. Based on these findings, RISS for multiple myeloma has been suggested [1]. Overall, 30% of patients had positive FISH results for five of the common genetic abnormalities screened. Lower yield of cytogenetic abnormalities in our group is owing to the use of limited FISH panel targeting RISS-defined high-risk cytogenetic abnormalities [6],[7]. Del 13q is the most common cytogenetic abnormality and t (14;16) was not detected in our study cohort. [Figure 2] shows distribution of cytogenetic abnormalities in our study cohort. RISS-defined high-risk abnormalities were seen in 10% of our patients. Studies by other groups such as Dhiman et al. [6] and Kadam Amare and colleagues found it to be 14 and 22%, respectively.Seven (10%) patients had high-risk karyotype, and LDH was raised in five (7.1%) patients. Overall, 34.2% of patients had change in risk stratification based on FISH and LDH results.
Figure 2 Spectrum of abnormalities in patients testing positive for myeloma FISH panel (n=21). FISH, fluorescent in situ hybridization. Conclusion IFE was highly sensitive in detecting M protein but does not quantify M band. In resource-constrained setting, using sFLC sequentially when SPEP is noninformative but UPEP/IFE shows M band can be a viable approach. However, sFLC will be indispensable for application of sLIM [S-60% or greater clonal plasma cells, Li-Light chain ratio>100 (involved/uninvolved) M-MRI>1 focal lesion] criteria for diagnosis when CRAB features are absent. FISH for high-risk karyotypic abnormalities was informative and helped in better prognostication of 34% of our patient group. Routine testing for high-risk cytogenetic abnormalities by FISH is of paramount importance.
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Nil.
Conflicts of interest
There are no conflicts of interest.
References
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