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"lazarus Response" When Feto-maternal Microchimerism Kicks In: Spontaneous Remission In Refractory Primary Mediastinal B Cell Lymphoma Following Twin Pregnancy

Tomai, R. 2024Lymphoma

Tomai, R. A., Iluta, S., Tigu, A. B., Nistor, M., Bancos, A., Cenariu, D., Jitaru, C., Patcas, S., Dima, D., Kegyes, D., Buruiana, S., Zdrenghea, M., Tanase, A. D., Tomuleasa, C., & Micu, R. (2024). "Lazarus Response" When Feto-Maternal Microchimerism Kicks in: Spontaneous Remission in Refractory Primary Mediastinal B Cell Lymphoma Following Twin Pregnancy. Diagnostics (Basel, Switzerland), 14(18), 2084. https://doi.org/10.3390/diagnostics14182084

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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.

Case Details

Disease Location

Mediastinum, lymph nodes

Personal Characteristics

27-year-old nulliparous female with a medical history of polycystic ovary syndrome and obesity

Clinical Characteristics

Opresented for progressive fatigue and shortness of breath with an onset two months prior and recent aggravation. Clinical examination revealed significant dyspnea, and history revealed onset of night sweats, fatigue, and unintentional weight loss of 10 kg within the last 2 months. Chest CT revealed a mediastinal mass. Mediastinotomy and tumor biopsy were performed, and the preliminary pathology report suggested malignant lymphoma. Laboratory test showed microcytic anemia, elevated ldh, alkaline phosphatase and inr. Neck, chest, abdomen and pelvis CT revealed multiple retroclavicular adenopathies and bilateral axillary and cervical adenopathies of up to 19mm and an interior mediastinal adenopathy block of 110/85mm, with invasion of the anterior thoracic wall and right pectoris muscle. There was a pleural effusion of 25mm and a pericardial effusion of 10mm. The pathology report showed a malignant neoplasia composed of medium to large pleomorphic cells and important tissue necrosis. A formal diagnosis of stage ii of primary mediastinal b cell lymphoma was made. She was treated according to the rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (r-da-epoch) regimen. After the 3rd cycle of chemoimmunotherapy, she developed a central line methicillin-resistant staphylococcus epidermidis (mrse) infection which required catheter and resolved under antibiotic therapy with vancomycin. After the infection chemotherapy was switched to rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (r-choep) regimen without response. The patient was started on second line treatment with rituximab, ifosfamide, carboplatin (r-ice). Upon evaluation she was discovered to be in the 6th week of amenorrhea and subsequently confirmed pregnant with twins.

Remission Characteristics

6 months later, in the 34th week of pregnancy, in seemingly good overall condition. Disease extension was assessed by thorax MRI which showed morphologic remission of tumor mass, with right mediastinal, paracardial encapsulated mass of 34/18 mm with central necrosis and minimal thoracic wall invasion.

Treatment & Mechanisms

Proposed Remission Mechanisms

The spontaneous remission of lymphoma in this case might be attributable an influence of feto-maternal microchimerism

Clinical Treatment

Mediastinomy, biopsy rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (r-da-epoch). Vancomicin rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (r-choep) rituximab, isofosmaide, carboplatin (r-ice)

Non-Clinical Treatment

None reported