"Lazarus Response" When Feto-Maternal Microchimerism Kicks in: Spontaneous Remission in Refractory Primary Mediastinal B Cell Lymphoma Following Twin Pregnancy

Abstract

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer.

Keywords: SRY; gene analysis; microchimerism; remission.

Figure 1

Computer tomography at diagnosis showing mediastinal adenopathy block (red arrows), with compression of vasculature (purple arrow) and invasion of thoracic wall and right pectoral muscle (blue arrows), pleural effusion (yellow arrows). Left side—ce reprezinta (descriere), Right side—ce reprezinta (descriere).

Figure 2

Electrophoresis for gDNA amplification of SRY. The SRY amplicon is 113 bp in length, and GAPDH is 89 bp in length. Male gDNA 100 ng—1; 75 ng—2; 50 ng—3; 25 ng—4; 10 ng—5; 1 ng—6; Female negative control gDNA—7; Patient DNA during pregnancy week 34 gDNA—8; patient DNA 4 years later—9.

Figure 3

SRY gene DNA quantification in gDNA via RT PCR. The red dots are the standard diluted samples, starting from 50 ng gDNA. The blue dots are the two positive SRY samples from patient in duplicate samples. A—Male control sample (50 ng/reaction); B—Female control sample (50 ng/reaction), C—Patient at 34 weeks of pregnancy (50 ng/reaction), D—Patient after 4 years (50 ng/reaction), ND—not detected. Left side—image depicting calibration curve and linearity for SRY determination, Right side—graphic depicting the comparison between gene amplification for SRY and housekeeping gene GAPDH (with the maximum determination at cycle 40).