Does Development of Plasmacytosis have a Role in Spontaneous Remission of Acute Myeloid Leukemia?

Dear editor,

We describe a 58-year-old male who was found to have leukocytosis, anemia and thrombocytopenia (hemoglobin 87 g/L, total leucocyte count 39.8 × 10⁹/L with 65% blasts and platelet count 37 × 10⁹/L) while being evaluated for a perianal abscess. Bone marrow examination with flow cytometry was done which showed 97% blasts, positive for CD13, CD117 and HLADR consistent with diagnosis of acute myeloid leukemia (AML)M0 (Fig. 1a). Cytogenetic or molecular analysis was not performed. Before he could be started on chemotherapy, he developed high grade fever and dry cough. Contrast enhanced computerized tomogram of chest revealed bilateral lung nodules and ground glass opacities with elevated serum galactomannan (1.8) suggesting fungal pneumonia. He was started on liposomal Amphotericin (3 mg/kg/day) and anti-leukemia therapy was deferred. While on anti-fungal treatment, he developed progressive pancytopenia with disappearance of peripheral blasts (hemoglobin 57 g/L, total leucocyte count 0.9 × 10⁹/L with no blasts on smear and platelet count 32 × 10⁹/L). As the patient had active disease, GCSF was not administered. Repeat bone marrow was done, 14 days following the first bone marrow examination. It was hypo-cellular with no excess blasts. Interestingly, it revealed 30% plasma cells (Fig. 1b). There was no monoclonal band, serum free light chain ratio was normal and flow cytometry did not reveal light chain restriction, consistent with reactive plasmacytosis. He was continued on supportive care only and received multiple packed red blood cell transfusions while targeting hemoglobin of > 80 g/L. Meanwhile, his peripheral blood counts started improving and he achieved near complete hematological recovery (hemoglobin 98 g/L, total leucocyte count 4.2 × 10⁹/L with no blasts on smear and platelet count 151 × 10⁹/L) at 7 weeks. Bone marrow was repeated on recovery of cell counts, 8 weeks after he underwent first bone marrow examination. It had normal cellularity with no excess of blasts or plasma cells suggesting spontaneous remission of AML. Six months later, he relapsed. He was started on Decitabine therapy but succumbed to infectious complications.

Fig. 1.

a Bone marrow aspirate showing blasts (encircled) b Bone marrow aspirate showing plasmacytosis (encircled)

Spontaneous remission in AML is a rare phenomenon and the mechanism has not been conclusively elucidated. Correlation of severe systemic infections and spontaneous remission in AML has been demonstrated previously. The activation of natural killer cells, as well as humoral factors including cytotoxic antibodies and hypergammaglobinemia have been proposed as possible mechanisms. Transfusion associated graft versus host disease imparting a graft-versus-leukemia effect leading to AML resolution is another postulated mechanism [1, 2]. Also, there have been reports of remissions induced by single agent GCSF without concurrent chemotherapy [3]. In this patient, a second bone marrow was done to confirm the diagnosis as circulating blasts had disappeared without anti-leukemia therapy. Thus, unknown to us at the time, we had a rare opportunity to demonstrate the interim marrow findings in a patient undergoing spontaneous remission of AML. This bone marrow revealed plasmacytosis with 30% polyclonal reactive plasma cells. Bone marrow plasmacytosis has been reported in AML and has been attributed to the interleukin 6 (IL-6) production by the myeloid blasts [4]. In most reports, plasmacytosis has been described at the time of presentation. Nada et al. had studied the clinical significance of plasmacytosis in day 14 (D14) marrow of patients with AML undergoing induction chemotherapy. They found a significant correlation between residual plasma cells in D14 marrow and antecedent infection. More importantly, they demonstrated that patients who had a greater proportion of plasma cells at D14 were more likely to be free of leukemia, the mechanism of which was possibly immune mediated [5]. In this case, we were able to demonstrate bone marrow plasmacytosis while the patient was undergoing spontaneous remission. This finding may impart credence to the immune mediated mechanism of spontaneous remission in AML. Further studies are needed to study the association of bone marrow plasmacytosis with remission in general and its relevance in cases of spontaneous remission of AML.

Author contributions

NJ, RN and SR conceived the idea and wrote the first draft. SS, NV and PM supervised, edited and wrote the final draft. All authors discussed the case and contributed to the final manuscript.

Funding

None.

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Conflict of interest

The authors declare no conflict(s) of interest.