Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2020; 12(11): 1288-1295
Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1288
Cancer-related microangiopathic hemolytic anemia in patients with advanced gastric cancer: A retrospective single-center analysis
Anne Katrin Berger, Michael Allgäuer, Leonidas Apostolidis, Anna Elisa Schulze-Schleithoff, Uta Merle, Dirk Jaeger, Georg Martin Haag
Anne Katrin Berger, Leonidas Apostolidis, Dirk Jaeger, Georg Martin Haag, Department of Medical Oncology, National Center for Tumor Diseases, University Hospital of Heidelberg, Heidelberg 69120, Germany
Michael Allgäuer, Department of Pathology, Institute of Pathology, University Hospital of Heidelberg, Heidelberg 69120, Germany
Anna Elisa Schulze-Schleithoff, Department of Gastroenterology, University Hospital of Heidelberg, Heidelberg 69120, Germany
Uta Merle, Department of Gastroenterology and Hepatology, University Hospital of Heidelberg, Heidelberg 69120, Germany
Author contributions: Berger AK completed conception and design, acquisition of data, analysis and interpretation of data, writing and revision of the manuscript; Allgäuer M and Apostolidis L finished analysis and interpretation of data, rewriting and review of the manuscript, technical support; Schulze-Schleithoff AE, Merle U and Jaeger D completed acquisition of data, writing and review of the manuscript; Haag GM finished conception and design, acquisition of data, analysis and interpretation of data, writing and review of the manuscript; All authors approved the final manuscript version.
Institutional review board statement: The study was approved by the local Ethics Committee University of Heidelberg, No. S-335/2014.
Informed consent statement: According to local ethics policy for retrospective analysis of own anonymized clinical data, informed consent was not obtained.
Conflict-of-interest statement: Haag MG has received fees for consulting or advisory role: Bristol-Myers Squibb, MSD Sharp & Dohme (Inst), EsoCap. Honoraria: Servier, MSD Sharp & Dohme. Research Funding: Nordic Pharma (Inst); Taiho Pharmaceutical (Inst), MSD (Inst). Travel, Accommodations: Bristol-Myers Squibb; Lilly, all outside the submitted work. Leonidas Apostolidis: reports grants, personal fees and non-financial support from Ipsen, personal and non-financial support from Novartis, all outside the submitted work. All other authors have no conflicts to declare.
Data sharing statement: The dataset is available from the corresponding author. 
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of item.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anne Katrin Berger, MD, Attending Doctor, Department of Medical Oncology, National Center for Tumor Diseases, University Hospital of Heidelberg, Im Neuenheimer Feld 460, Heidelberg 69120, Germany. anne.berger@med.uni-heidelberg.de
Received: July 7, 2020
Peer-review started: July 7, 2020
First decision: September 17, 2020
Revised: September 27, 2020
Accepted: October 19, 2020
Article in press: October 19, 2020
Published online: November 15, 2020
Processing time: 127 Days and 17.2 Hours
Abstract
BACKGROUND

Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia and organ failure caused by tumor-associated thrombotic microangiopathy (TMA) is a life-threatening oncological emergency. Rapid diagnosis and precise distinction from other forms of TMA is crucial for appropriate therapy, which aims at treating the underlying malignancy. However, the prognosis of patients with cancer-related (CR)-MAHA is limited. To date, less than 50 patients with gastric cancer and CR-MAHA have been reported, mainly as single case reports, and detailed information on treatment strategies and outcome are scarce. We analyzed the characteristics and outcomes data of CR-MAHA patients with gastric cancer treated at our center between 2012 and 2019.

AIM

To gain knowledge about CR-MAHA and the course of disease.

METHODS

We retrospectively analyzed patients using an institutional prospectively maintained database. Patients who had CR-MAHA but other cancer types or cancer of unknown primary were excluded. The basic requirements for inclusion were: Histologically proven gastric adenocarcinoma; and clinical diagnosis of hemolytic anemia with schistocytes with or without thrombocytopenia. The observation period for each patient started with the first day of documented symptoms. The follow-up period for this analysis ended on February 1, 2020.

RESULTS

We identified eight patients with a median age of 54 years. Histologically, all patients had (partial) diffuse subtypes of gastric adenocarcinoma with partial or complete signet cell morphology. All patients had metastatic disease and one patient had a microsatellite instability-high (MSI-H) tumor. In three patients, clinical signs of MAHA preceded the diagnosis of cancer, and in two patients, CR-MAHA indicated recurrent disease. All patients had severe hemolytic anemia and thrombocytopenia. Six patients experienced severe bone pain, and five patients had dyspnea. Systemic, 5-fluorouracil-based combination chemotherapy was initiated in six patients, which resulted in rapid initial response with significant improvement of clinical symptoms and blood values. Progression-free survival (PFS) of the whole cohort was 1.9 wk and median overall survival (OS) was 1.9 wk. For patients with chemotherapy, PFS was 9.0 wk and OS was 10.3 wk. The patient with the MSI-H tumor has been undergoing immunotherapy for more than 3 years.

CONCLUSION

The benefit of chemotherapy in CR-MAHA patients is limited. Immunotherapy for patients with MSI-H tumors may lead to long-term tumor control even in CR-MAHA patients.

Keywords: Microangiopathic hemolytic anemia; Gastric cancer; Chemotherapy; Second-line chemotherapy; Thrombocytopenia; Microsatellite instability-high tumor

Core Tip: Microangiopathic hemolytic anemia (MAHA) with thrombopenia and organ failure caused by tumor-associated thrombotic microangiopathy is a rare and life-threatening oncological emergency. The only proven therapy is the treatment of the underlying malignancy. In our retrospective series, 6 of 8 cancer-related (CR)-MAHA patients with advanced gastric cancer received combination chemotherapy with an overall survival (OS) of 10.3 wk. For the whole cohort, OS was only 1.8 wk. Second-line treatment did not show any benefit. One patient with microsatellite instability-high tumor has been undergoing immunotherapy for more than 3 years, which to the best of our knowledge is the first reported case of long-term survival in a CR-MAHA patient with advanced disease.