Bactrim: “CRAB” Findings in a Patient With Fatigue and Poor Appetite

Possible Answers

Most likely diagnosis: multiple myeloma. Multiple myeloma is defined as a clonal proliferation of aberrant bone marrow plasma cells accompanied by monoclonal protein production and destructive bone lesions.[1]

The most common clinical manifestations of multiple myeloma are summarized by the acronym, "CRAB": hypercalcemia, renal dysfunction (ie, increased serum creatinine concentration), anemia, and lytic bone lesions.[2] The most recent diagnostic criteria for multiple myeloma are summarized in Table 2 .[2]

Although monoclonal protein spikes (M-spikes) are most often seen upon SPE or UPE of serum or urine from patients with a plasma cell dyscrasia, they can also be seen upon SPE of serum and/or urine from patients with lymphoma, carcinoma, chronic infections, solitary and multiple plasmacytomas, plasma cell leukemia, amyloidosis, smoldering (or indolent) myeloma, and monoclonal gammopathy of undetermined significance (MGUS).[2,3] Interestingly, non-secretory multiple myeloma is associated with an absence of an M-spike(s) by SPE, UPE, or IFE.

In 1999, a panel of experts published 9 guidelines for the clinical and laboratory evaluation of patients with monoclonal gammopathies[4] that are summarized in Table 3 .

Despite the fact that the patient had no evidence of residual disease on examination of her bone marrow, she continued to have an abnormal serum protein electrophoresis pattern (SPEP). Moreover, the SPEP originally seen on electrophoresis of her serum had changed significantly from a single IgG kappa M-protein to an oligoclonal pattern consisting of IgG kappa, IgG lambda, and free lambda light chains. It is likely that the patient's markedly decreased platelet count and modestly decreased hemoglobin and hematocrit values ( Table 1 ) were due to continued bone marrow recovery following melphalan therapy and stem cell transplantation.

Transient oligoclonal (ie, ≥2 M-protein bands on SPEP) and monoclonal gammopathies occur in at least 50% of all patients after stem cell transplant and in at least 10% of patients with multiple myeloma treated with stem cell transplant.[3,6] These bands have been shown to appear between 2 to 6 months post-stem cell transplant and persist on SPEPs for an average of 6 months.[3]

When oligoclonal bands or a monoclonal band with a different immunophenotype than the band observed initially are observed, the differential diagnosis includes a change in M-protein production by the original plasma cell clone, the emergence of a second malignant clone, or the evidence for immune system regeneration following stem cell transplant therapy. To date, most studies favor the latter hypothesis; the bands represent a benign phenomenon associated with the recovery of immune function in patients who have received a stem cell transplant with or without myeloablative bone marrow therapy prior to stem cell transplantation.[3,6-8]One study of patients with multiple myeloma who were treated with stem cell transplantation, with or without prior myeloablation, revealed a significant relationship between the appearance of abnormal protein bands by SPE and IFE after transplantation and a higher likelihood of positive clinical response, event-free survival, and overall survival.[6]

For more than 2 decades, the standard therapy for patients with symptomatic multiple myeloma has included a wide variety of chemotherapeutic regimens. The most commonly used regimens include combined melphalan and prednisone therapy and the combination of vincristine, adriamycin, and dexamethasone (VAD).[1] Such treatments are associated with a median survival of 2 to 3 years. Other chemotherapeutic regimens, which have been used as both frontline and relapse therapies, include pulse dexamethasone and combined therapy with thalidomide and dexamethasone.[1] Unfortunately, almost all patients who initially respond to chemotherapy eventually relapse. In recent years, high-dose chemotherapy followed by autologous stem cell transplantation has become an important alternative frontline treatment for younger patients (<70 years) as well as a rescue therapy for patients who relapse after chemotherapy. This treatment achieves higher complete response rates compared to chemotherapy alone. Prolonged survival (>6 years), however, remains rare.[9]  Printer- Friendly Email This

Lab Med.  2005;36(8):482-485.  ©2005 American Society for Clinical Pathology
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