Spontaneous Regression Of Intravascular Large B-cell Lymphoma And Apoptosis Of Lymphoma Cells: A Case Report
Takahashi, T., Ikejiri, F., Takami, S., Okada, T., Kumanomidou, S., Adachi, K., Yumi, J., Onishi, C., Kawakami, K., Moriyama, I., Inoue, M., Miyake, T., Tanaka, J., Maruyama, R., & Suzumiya, J. (2015). spontaneous Regression of Intravascular Large B-Cell Lymphoma and apoptosis of Lymphoma Cells: A Case report. Journal of clinical and experimental hematopathology : JCEH, 55(3), 151–156. https://doi.org/10.3960/jslright.55.151
View Original Source →Abstract
A 61-year-old Japanese woman presented with hemophagocytic syndrome (HPS) and suffered from intravascular large B-cell lymphoma (IVLBCL). After a few days of supportive care, her condition improved without any anti-cancer drugs or steroids. She experienced recurrences of HPS at 15 mon and 21 mon after first presentation, but lymphoma cells were not observed. Relapse of IVLBCL with pulmonary involvement occurred 27 mon after first presentation. She underwent R-CHOP therapy followed by autologous stem cell transplantation. She is currently alive and without lymphoma. Immunostaining by anti-ssDNA suggested that spontaneous regression may have been due to apoptosis of the lymphoma cells.
Case Details
Disease Location
Intravascular large b-cell lymphoma with pulmonary involvement
Personal Characteristics
61 -year-old female japanese had been treated with amoxicillin for palmoplantar pustulosis 5 years previously
Clinical Characteristics
Presented with hemophagocytic syndrome (hps) and suffered from intravascular large b-cell lymphoma (ivlbcl) admitted with a a fever and appetite loss CT scan showed hepatosplenomegaly lab exam showed leukocytopenia (2.24x10^4/ul) and increased serum levels of aspartate aminotransferase (374 iu/l), alanine aminostransferase (315 iu/l), ldh (2,535 iu/l), alkaline phophatase (1,037 iu/l), and c-reactive protein (2.9mg/dl) serum titers of anti-ebv antibodies showed viral capsid antigen-IGG x80, ebv-associated antigen x10, and viral capsid antigen-IGM < x10 bone marrow smear (1st bone marrow exam) showed infiltration of abnormal lymphocytes and proliferation of immature monocytes with hemophagocytosis, bone marrow clot specimen showed a growth of abnormal lymphocytes within the lumina of the vessels. Ivlbcl was diagnosed her performance status was 1 and was carefully monitored with supportive care i.e. Oral acetaminophen for fever and IV infusion of saline for dehydration on the third day of admission her symptoms disappeared and lab data returned to normal the 2nd bone marrow 2 weeks after admission showed no evidence of abnormal cells 15 months after first admission, she then re-presented with initial symptoms again plus thrombocytopenia and elevated ast, alt, and ldh CT scan showed hepatosplenomegaly, 3rd bone marrow biopsy showed hemophagocytosis, but no abnormal lymphocytes that time. Supportive care was initiated after she remained stable for 6 months, she presented again at 21 month after first admission with similar symptoms as the first admission. The 4th bone marrow biopsy showed hemophagocytosis without lymphoma cells, but this time her condition did not improve with supportive care. Oral prednisolone for 2 months improved her symptoms as she tapered the prednisolone, she worsened. She complained of fever, dry cough, and dyspnea at 27 months after first presentation. CT scanshowed bilateral pulmonary infiltration lung biopsy specimens and a 5th bone marrow biopsy showed infiltration of large b-cell lymphoma cells in the vessels and released lymphoma was diagnosed. She recieved 8 courses of r-chop 1 year after the start of r-chop, she complained of general fatigue and appetite loss, thrombocytopenia and elevated ldh reappeared. CT showed only splenomegaly and the 6th bone marrow biopsy confirmed relapsed ivlbcl she received 2 courses of chaser but didn't achieve complete remission, so she then underwent 2 courses of r-ice she then received high dose chemo (mcec) followed by an autologous peripheral blood stem cell transplantion during the second complete remission ( double click to enhance cell) the 1st bone marrow exm showed hypercellularity (70%) and large atypical lymphoid cells within the lumina of the vessels with hemophagocytosis. Ihc staining showed abnormal lymphoid cells within the lumina were positive for CD5, 20, bcl-2, and mum-1 the 2nd-4th bone marrow biopsies within 27 months of first presentation showed no lymphoma the lung biopsy at 27 months after first presentation showed growth of large lymphoma cells in the capillary vessels of the alveolus and pleura, additionally the 5th bone marrow biopsy at the same time showed lymphoma cells in the vessels ihc revealed the lymphoma at relapse had the same phenotypes as those at the first presentation mib-1 labeling index at the 1st and 5th marrow biopsies was 80% g-banding chromosomal analysis of lymphoma cells in the lung tissue showed: 49,xx,-1,+3,del(6)(q?),+9,+add(12)(p11.2)add(12)(q13),-13,-19,-19,-20,+rl,+mar1,+mar2,+mar3,+mar4,+mar5 in 15 of the 20 cells examined
Remission Characteristics
Lab data returned to normal and symptoms disappeared on third day of admission 2nd bone marrow exam including histologic exam and flow cytometry showed no evidence of abnormal cells 2 weeks after admin after a week of supportive care from her 2nd admission 15 months later, her condition recovered. She remained stable for 6 months thrombocytopenia, ast, alt, and ldh serum levels improved after oral prednisolone at the 3rd admission r-chop led to complete remission, symptoms disappeared and serum levels of ldh, ast, and alt normalized after r-ice complete remission was achieved 6 years after first presentation, she was alive and without lymphoma or serious complications
Treatment & Mechanisms
Proposed Remission Mechanisms
Sr may depend on apoptosis and immune system activity, as well as the conditions of the tumor microenvironment case details suggest sr not related to immune system activity primary mechanism of sr in this case is suggested to be likely related to apoptosis
Clinical Treatment
Oral acetaminophen and IV saline oral prednisolone r-chop (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chaser (cyclophosphamide, high dose cytarabine, dexamethasone, etoposide, and rituximab) r-ice rituximab, ifosphamide, caboplatin, and etoposide) mcec (ranimustine, caboplatin, etoposide, and cyclophosphamide) autologous peripheral blood stem cell transplantation
Non-Clinical Treatment
None reported