Risk factors for non-infectious diarrhea of patients with multiple myeloma after chimeric antigen receptor T- cell immunotherapy: A retrospective observational study

doi:10.21203/rs.3.rs-2985897/v1

Download PDF

Research Article

Risk factors for non-infectious diarrhea of patients with multiple myeloma after chimeric antigen receptor T- cell immunotherapy: A retrospective observational study

https://doi.org/10.21203/rs.3.rs-2985897/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Aims

Patients with multiple myeloma after chimeric antigen receptor T-cell immunotherapy suffered from diarrhea. Recurrent diarrhea further conversely decreases nutritional status

Methods

This study enrolled 88 patients with multiple myeloma who received chimeric antigen receptor T-cell immunotherapy at one tertiary general hospital in China. Participants were categorized into diarrhea subgroup and non-diarrhea subgroup according to the occurrence of diarrhea. Demographic data and self-reported measurements and planning were obtained from questionnaires and clinical data from hospital databases.

Results

In total, 50 patients suffered from non-infectious diarrhea, with the prevalence of 56.8%. Multiple logistic regression analysis showed that severe cytokine release syndrome (OR = 5.980), underlying diseases (OR = 4.184), previous treatment lines ≥ 6 (OR = 6.292) were prominent hazardous factors for non-infectious diarrhea (p < 0.05).

Conclusions

The incidence rate of non-infectious diarrhea in patients with multiple myeloma after CAR-T therapy was at a high level. Severe cytokine release syndrome, previous treatment lines ≥ 6 and the underlying diseases were important predictors for non-infectious diarrhea. Medical staff should early evaluate these major factors to reduce the risk of diarrhea.

Multiple Myeloma

Chimeric Antigen Receptor T-cell Therapy

Diarrhea

Risk Factors

Multiple myeloma (MM) is a rare type of blood cancer that develops in bones and other area of the body. It results when certain cancerous cells-called myeloma cells-build up in the bone marrow [1], accounting for 13% of hematological malignancies, following in lymphoma [2]. MM currently is incurable, and it easily leads to the stage of recurrence and refractory with a grave prognosis. According to 2021 American cancer statistic, the fatality rate of MM has been up to 90% in recent five years [3]. Obviously, MM brings about considerable psychological and economic burden for patients and their families.

As a revolutionary new immunotherapy in the field of anti-tumor, chimeric antigen receptor T-cell therapy (CAR-T) becomes a novel alternative treatment strategy that can combat with chemotherapeutic resistance. Compared with traditional chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT), CAR-T therapy embraces stronger operability and wider application [4]. Emerging studies support the good effectiveness and safety of CAR-T therapy on the population with relapsed / refractory MM [5–6]. A meta-analysis reported that the survival rate of MM patients within 12 months after CAR-T therapy reached to 78% [7]. Moreover, Guo et al. found that among five patients with relapsed/refractory MM who received CD138z CAR-T therapy, four patients were in stable disease longer than three months, one patient with advanced plasma cell leukemia had a reduction of the myeloma cells in her peripheral blood (from 10.5–3%) [8].

However, the side effects caused by CAR-T treatment are not negligible, such as cytokine release syndrome (CRS), off-target effects, neurotoxicity, diarrhea, etc [9]. Of these adverse reactions, non-infectious diarrhea is one of the most commonly reactions, this is a gastrointestinal illness characterized by the change of frequency (≥ three times) and shape of defecation [10]. Non-infectious diarrhea usually is after secondary to CRS [11–12]. MM patients secrete excessive abnormal immunoglobulin of malignant plasma cells that invade tissues and organs as well as inhibit the hematopoietic function of bone marrow, and the low immunity of middle-aged and the elderly, thus MM people with diarrhea have an increased risk of infection [13]. Persistent and severe diarrhea may lead to perianal infection. Luo et al. employed a case-control study to investigate the risk factors for perianal infection in patients with hematological tumor, and found that diarrhea was one of the significant elements [14]. Also, the consequences of acute diarrhea extend beyond dehydration and electrolyte imbalance, nutritional disorder, or even death, which menaces the quality of life and life cycle of MM patients [15].

Up to now, little known about the risk factors for the non-infectious diarrhea among MM patient with CAR-T therapy, paying more attention to this is of great significance to improve the prognosis and treatment of MM patients. The main aim of this study is to ascertain the risk factors and prevalence of non-infectious diarrhea of MM patients during CAR-T therapy.

Study design and setting

This is a retrospective observational study, the present study recruited 88 consecutive patients who underwent multiple myeloma and received CAR-T therapy from the Center for Hematology and Bone Marrow Transplantation of The First Affiliated Hospital, Zhejiang University School of Medicine, China, between July 2018 and September 2021.

Participants and data collection

Criteria for selecting the subjects were as follows: a) diagnosed as multiple myeloma according to Chinese Guideline for Diagnosis and Treatment of Multiple Myeloma [16]; b) ≥ 18 years old; c) treated with BCMA CAR-T therapy; d) volunteered to participate in this study and signed an informed consent prior to the study. Participants who had a history of digestive tract reconstruction or were subjected to diseases accompanied with diarrhea were eliminated.

Demographic data were obtained from questionnaires and clinical data from electronic medical record (EMR) system. The questionnaires, which collected demographic information (age, sex, BMI, course of disease, etc.) and clinical data (Durie-Salmon staging, Durie-Salmon typing, previous treatment lines, type of monoclonal immunoglobulin, etc.) were personally administered at inpatient facilities. All members of this program received the training sessions regarding utilization of measures and data collection, and both of them were proficient in EMR system and assessment tools. In the course of data input and analysis, this study was supervised by two professionals per one or two weeks.

Instruments

Sociodemographic and clinical characteristics

The demographic data of all participants were collected for the following variables: gender, age, weight and height. In addition, clinical data, including diagnosis, Durie-Salmon staging, Durie-Salmon typing, previous treatment line, severity of CRS, a history of autologous transplantation, time of hospitalization, performance status, were extracted from EMR system.

Non-infectious diarrhea

According to the industry standard of Ministry of Health of the PRC [17], non-infectious diarrhea refers to bowel movements are more than three times per day without abdominal pain or fever, and stool routine results indicated normal.

Performance status

Physical State of Eastern Cooperative Oncology Group (ECOG) [18] was compiled by Eastern Cooperative Oncology Group, which is widely used in patients with cancer. Patients are asked to select the statement that was closest to their own current state of physical ability and activity. There are five degrees, which ranged from “I am fully active and able to carry out activities as I did before my cancer diagnosis, without any restriction” to “I am completely disabled, cannot carry on my self-care, and I am confined to a bed or chair”. The higher levels, the worse physical state.

Cytokine Release Syndrome

Grading for CRS [19] was made by American Society for Transplantation and Cellular Therapy (ASTCT) The main indicators include fever, hypotension and hypoxia. Grade 1 indicates the temperature of patients ≥ 38℃; grade 2 shows the low-flow nasal catheter oxygen inhalation (oxygen flow ≤ 6 L/min) based on the level 1; grade 3 represents that patient’s body temperature ≥ 38℃ and requires the use of vasopressin and high-flow nasal catheter, mask or Venturi inner mask. The difference between grade 4 and grade 3 is that hypoxia requires positive pressure ventilation, such as CPAP, BiPAP, intubation and mechanical ventilation; grade 5 means death of patient. Severity of CRS ≥ grade 3 indicates severe.

Nutritional status

Body Mass Index (BMI) is an important index recommended by WHO to evaluate the nutritional status of the body. Calculation method: BMI = weight (kg)/ height (m)2. According to Chinese adults, BMI < 18.5, 18.5–23.9, 24.0−27.9 and BMI ≥ 28.0 indicate low weight, normal, overweight and obesity, respectively [20].

Data analyses

The Statistical Package for the Social Sciences version 25.0 (IBM Corporation, Armonk, NY, USA) was used to process and analyze data. Descriptive statistics was employed to analyze clinical and demographic data of patients. Univariate analysis was used to test the relationships between sociodemographic and clinical parameters, non-infectious diarrhea. Based on the results of univariate analysis, multiple logistic regression analysis further identified the risk factors for non-infectious diarrhea. All analyses considered two-tailed p value of < 0.05 to be statistically significant.

Ethical consideration

Ethical and operational approval for this study was granted by the Institutional Review Board of The First Affiliated Hospital, Zhejiang University School of Medicine (Approval Number: ChiCTR1800017404).

Sample characteristics

In told, 88 patients who had received CAR-T therapy were recruited for this study through convenience sampling. Among these participants, 55 were male (62.5%), 33 were female (37.5%), with a mean age of 57.9 years (SD = 7.4). 55 (62.5%) had autologous transplantation; 19 (21.6%) had treatment lines ≥ 6; 54 (29.82%) had diarrhea. The characteristics of patients is shown in Table 1.

Table 1

Sociodemographic and clinical characteristics of patients with MM (n = 88)
Items	Mean ± SD / Median / Frequency (%)
Age (year)	57.9 ± 7.4
BMI	23.5 ± 2.6
Duration of disease (month)	28.5 (12.8–61.8)
Gender
Male	55 (62.5)
Female	33 (37.5)
The type of monoclonal immunoglobulin
IgA	24 (27.3)
IgD	6 (6.8)
IgG	35 (39.8)
Light chain	20 (22.7)
Nonsecretory	1 (1.1)
Other	2 (2.3)
DS staging
StageⅠ	2 (2.3)
Stage Ⅱ	9 (10.2)
Stage Ⅲ	76 (86.4)
NA	1 (1.1)
DS typing
Type A	62 (70.5)
Type B	15 (17.0)
NA	11 (12.5)
Performance status
Level 0	9 (10.2)
Level 1	32 (36.4)
Level 2	30 (34.1)
Level 3	5 (5.7)
NA	12 (13.6)
Extramedullary focus
Yes	51 (58.0)
No	37 (42.0)
Previous autotransplantation
Yes	33 (37.5)
No	55 (62.5)
Previous treatment lines
< 6	69 (78.4)
≥ 6	19 (21.6)
Severity of CRS
< grade 3	52 (59.1)
≥ grade 3	36 (40.9)
Use of tocilizumab
Yes	30 (34.1)
No	58 (65.9)
Diarrhea
Yes	54 (61.4)
No	34 (38.6)
Duration of diarrhea (day)	5.0 (1.0–8.0)
Interval between diarrhea and CAR-T cell reinfusion (day)	6.0 (4.0–12.0)
Interval between diarrhea and CRS (day)	4.0 (2.0–6.0)
Time of hospitalization (day)	25.0 (17.8–40.8)
Note: CRS, Cytokine release syndrome; BMI, Body Mass Index; NA, Not applicable; DS, Durie-Salmon.

Incidence rate of non-infectious diarrhea related to CAR-T therapy in MM patients

Of these patients with MM in the current study, 54 occurred diarrhea. the incidence rate of non-infectious diarrhea was 56.8%, including 29 males (58.0%) and 21 females (42.0%), with an average age of 58.3 years (SD = 8.5). The differences between diarrhea subgroup and non-infectious diarrhea subgroup are set out in Table 2.

Table 2

Comparation of sociodemographic and clinical characteristics between non-diarrhea subgroup and non-infectious diarrhea subgroup (n = 84)
Items	Non-diarrhea subgroup (n = 34)	Non-infectious diarrhea subgroup (n = 50)	t/χ²	p
Age (year)	58.2 ± 7.8	58.3 ± 8.5	-0.024 ^a	0.981
BMI	22.9 ± 2.29	23.9 ± 2.51	-0.946 ^a	0.347
Course of disease (month)	26 (12–87)	37.5 (18 − 5.8)	0.668 ^a	0.496
Gender			0.382 ^b	0.537
Male	22	29
Female	12	21
The type of monoclonal immunoglobulin			7.043 ^b	0.217
IgA	12	11
IgD	4	2
IgG	13	19
Light chain	5	15
Nonsecretory	0	2
DS staging			3.818 ^b	0.701
StageⅠ	1	1
Stage Ⅱ	4	5
Stage Ⅲ	29	43
NA	0	1
DS typing			5.453 ^b	0.141
Type A	23	36
Type B	4	10
NA	7	4
Performance status			4.253 ^b	0.373
Level 0	6	3
Level 1	11	20
Level 2	9	18
Level 3	3	2
NA	5	7
Extramedullary focus			0.954 ^b	0.329
Yes	22	27
No	12	23
Underlying diseases			2.299 ^b	0.129
Yes	17	27
No	17	23
Previous autotransplantation			0.086 ^b	0.77
Yes	14	19
No	20	31
Previous treatment lines			5.390 ^b	0.02
< 6	31	35
≥ 6	3	15
Severity of CRS			10.441 ^b	0.001
< level 3	27	22
≥ level 3	7	28
Use of tocilizumab			13.089 ^b	<0.001
Yes	4	25
No	30	25
Duration of diarrhea (day)	24 (17.3–39.5)	36.5 (24–46)	-2.631 ^a	0.01
Note: ^a, Independent t-test sample; ^b, χ² test; CRS, Cytokine release syndrome; BMI, Body Mass Index; NA, Not applicable; DS, Durie-Salmon.

Predictors of non-infectious diarrhea in MM patients

We eliminated participants with the infectious diarrhea and divided the remining participants into non-infectious diarrhea subgroup and non-diarrhea subgroup. Single factor analysis indicated that severity of CRS (p = 0.001), previous treatment lines ≥ 6 (p = 0.020), use of tocilizumab (p < 0.001) as well as length of hospitalization (p = 0.010) were statistically significantly correlated with non-infectious diarrhea in patients with MM (see Table 2).

With non-infectious diarrhea as dependent variable, these factors with statistical significance in the single factor analysis were included in the multiple logistic regression analysis. The results, as shown in Table 3, represented that severity of CRS (OR = 6.292, p = 0.002), previous treatment lines ≥ 6 (OR = 5.980, p = 0.028) and underlying diseases (OR = 4.184, p = 0.017) were major hazardous factors.

Table 3

The result of multiple logistic regression analysis of predictors for non-infectious diarrhea in MM patients
Variable	B	SE	Wald’s value	p	OR	95% CI
Severity of CRS	1.839	0.592	9.659	0.002	6.292	1.973–20.067
Previous treatment lines	1.788	0.814	4.824	0.028	5.980	1.212–29.493
Underlying diseases	1.431	0.598	6.937	0.017	4.184	1.296–13.505
Note: SE, Standard error.

To our knowledge, this is the first study to explore the risk factors for non-infectious diarrhea in MM patients who treated with CAR-T therapy. The incidence rate of non-infectious diarrhea (56.8%) of MM patients during CAR-T therapy overall was at a high level in this study. This result may partly be explained by chemotherapeutic regimens. It is well known that bortezomib, lenalidomide and pomalidomide, recommended for the treatment of relapsed MM in the Chinese Guideline for Diagnosis and Treatment of Multiple Myeloma [16], are used as the first choice for the chemotherapy protocols of the participants. However, when acting on gastrointestinal epithelial cells, these chemotherapeutic agents can lead to the destruction on normal function of intestinal mucosa and the imbalance of intestinal flora, further inducing diarrhea [21–22]. Another possible explanation for this is that it may be related to the utilization of chemotherapeutic and immunosuppressive agents that can cause diarrhea, nausea, vomiting and gastrointestinal reactions. In addition, myeloma cell infiltration associated with digestive system amyloidosis and coagulation disorders are able to set off gastrointestinal symptoms [23]. The average age of the participants in this study was 57.9 years. A study reported that advanced age was one of the most risk factors for diarrhea, the immunity and gastrointestinal absorption function would deteriorate with aging [24]. In view of the above factors, nurses should positively master the theoretical knowledge related to CAR-T therapy and improve the cognition of adverse outcomes of non-infectious diarrhea, especially the early screening and evaluation of risk factors for non-infectious diarrhea.

In the course of CAR-T treatment, CRS is one of the most widely common complications and a prominent cause of diarrhea. The finding of this study showed that there was a statistically significant difference in the severity of CRS between non-infectious diarrhea subgroup and non-diarrhea subgroup (p < 0.05). Zeng et al. [25] found that diarrhea was a marked manifestation of CRS via the observation on a sample of 95 patients with relapsed / refractory B-cell lymphoma, which was similar to our finding. Generally speaking, CRS occurs within 1–2 weeks after CAR-T cell reinfusion [26]. The data of the present study suggested that the duration of non-infectious diarrhea was about 5 (1.8–14) days, with an interval of 4 (2−6.5) days from the first day of CRS, which almost coincided with the period of CRS response. CRS is always accompanied by the release of a large number of cytokines, especially interleukin−6 (IL−6) and tumor necrosis factor-α (TNF-α) [27]. IL−6 and TNF-α will induce diarrhea by increasing intestinal permeability to weaken the intestinal defense function. Hence, after the reinfusion of CAR-T cells, clinical staffs need to ascertain the omens of CRS responses among MM patients and timely control the development of CRS to reduce the emergency of non-infectious diarrhea.

The current study found that the risk of non-infectious diarrhea in patients with ≥ 6 treatment lines was 5.98 times higher than that in patients with < 6 treatment lines. MM is an incurable plasma cell tumor with high recurrence. Repeated episodes can stimulate individual’s drug resistance mechanism, strengthen resistant ability and increase the treatment lines. As the first-line drugs for the treatment of relapsed MM, bortezomib, lenalidomide and thalidomide easily produce adverse reactions [16]. A real-world prospective study in a group of patients with relapsed/refractory MM pointed out that diarrhea was the second most common side effect caused by bortezomib, with an incidence rate of 17% [28]. Another study on lenalidomide + bortezomib + dexamethasone in the treatment of recurrent/ refractory MM also deemed that diarrhea (60%) was a major adverse reaction [29]. It is undeniable that comprehending the patient’s previous medication and treatment plans in detail as well as strengthening drug disposal management are paramount.

Also, our study found that underlying illnesses were the strong predictor of non-infectious, the risk of non-infectious diarrhea in patients with underlying diseases was 4.18 times higher than that in patients without underlying diseases. In accordance with the present study, Shi et al. demonstrated that primary illnesses were a significant element of diarrhea in ICU patients [30]. Majority participants suffered from hypertension, diabetes, cardiovascular and respiratory diseases and renal dysfunction. Due to the chronic hyperglycemia and the worse glucose regulation, the accumulation of hyaluronidase gradually induces a significant thickening of the duodenal wall and a narrowing of the lumen, poorly interfering with the absorption of nutrients, water and electrolytes. In addition, 41.7% of the patients in this study were over 60 years old with the unstable conditions. For those with advanced age and primary diseases (e.g., hypertension and diabetes), the more severe the performance, the worse the functional status [31]. Therefore, nurses need to analyze the possible synergistic effects between different diseases from the perspective of holistic nursing and actively show solicitude for the physiological indicators.

Limitations

The generalizability of these findings is subject to certain limitations. First, the sample only came from one site. It is necessary to enlarge the source of sample, further conducting the multi-center, large-scale investigations. Second, this study focused on exploring the physical factors of non-infectious diarrhea, except for the psychological factors. Previous studies reported that long-term psychological stress and anxiety can also evoke non-infectious diarrhea [32]. Hence, following studies should incorporate psychological-related variables and analyzing the influence of psychological factors on non-infectious diarrhea of MM patients received CAR-T treatment.

In this study, the incidence of non-infectious diarrhea (56.8%) in MM patients after CAR-T treatment was at a high level. Severe CRS, treatment lines ≥ 6, underlying diseases are crucial risk factors of non-infectious diarrhea in MM patients. According to these findings, it is highly needed for nurses to pay close attention to the underlying diseases, earlier treatment protocols and medical records and vital signs. In order to reduce adverse outcomes caused by non-infectious diarrhea, effective assessment and targeted nursing intervention are imperative.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of The Affiliated First Hospital of Zhejiang University School of Medicine in Zhejiang Province, China (Approval No. 2021-104). In this study, all methods were performed in accordance with STROBE Statement and Declaration of Helsinki. Prior to the current study, all participants signed an informed consent and were informed of the right to withdraw from the research.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analysed during this study are included in this published article

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the Medical Science and Technology Project of Zhejiang Provincial Health Commission (Grant No. 2023KY709).

Author Contributions

Yongxian Hu and Mingming Zhang critically revised the draft. Aiyun Jin supervised the study procedure. Shuyi Ding and Yin Cheng was responsible for the literature review and manuscript writing. Jiali Yan was responsible for literature review. Linqin Wang and Houli Zhao contributed to statistical analyses. Nian Liu, Rui Wang, Sangsang Chen, Yijie Huang and Xin Gao were responsible for the data collection. Tianli Teng contributed to data scrutiny. All authors contributed to the article and approved of the submitted version.

Acknowledgements

The authors wish to thank the full support from the faculty members.

Bladé J, Cibeira MT, Fernández De Larrea C, Rosiñol L. Multiple myeloma. Ann Oncol. 2010; 21(7): 313-319. https://doi.org/10.1093/annonc/mdq363
Cowan AJ, Tuazon SA, Portuguese AJ, Green DJ. Chimeric antigen receptor T cells for multiple myeloma: the journey so far-and the road ahead. Cancer J. 2021; 27(2): 112-118. https://doi.org/10.1097/ppo.0000000000000506
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7-33. https://doi.org/10.3322/caac.21654
Xia L, Wang YY. Chimeric antigen receptor T-cell immunotherapy and its applications in hematological malignancies immunotherapy. Journal Of Shanghai Jiao Tong Univeristy (Medical Science). 2017; 37(6): 823-829+822. https://doi.org/10.3969/j.issn.1674-8115.2017.06.019
Wang D, Wang J, Hu G, et al. A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma. Blood. 2021; 137(21): 2890-2901. https://doi.org/10.1182/blood.2020008936
Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019; 380(18): 1726-1737. https://doi.org/10.1056/NEJMoa1817226
Yang Q, Li X, Zhang FR, Yang QH, Zhou W, Liu J. Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis. Int J Med Sci. 2021; 18(8): 1786-1797. https://doi.org/10.7150/ijms.46811
Guo B, Chen MX, Han QW, et al. CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. Transplant Cell Ther. 2016; 2(1): 28-35. https://doi.org/10.1016/j.jocit.2014.11.001
Hasegawa K, Hosen N. Chimeric antigen receptor T cell therapy for multiple myeloma. Inflamm Regen. 2019; 39: 10. https://doi.org/10.1186/s41232-019-0100-6
Frese T, Klauss S, Herrmann K, Sandholzer H. Nausea and vomiting as the reasons for encounter in general practice. J Clin Med Res. 2011; 3(1): 23-29. https://doi.org/10.4021/jocmr410w
Yan ZL, Li ZY, Xu KL. Chimeric antigen receptor T cells for hematological malignancies: current understanding and future challenge. Chin J Intern Med. 2019; 58(11): 793-795.
June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018; 379(1): 64-73. https://doi.org/10.1056/NEJMra1706169
Chen WL, Yao JX, Yang Y, Wang S, Liu B. Correlation between MBL gene polymorphisms and infection in multiple myeloma patients during chemotherapy. Chin J Nosocomiol. 2022; 17: 2662-2666. https://doi.org/10.11816/cn.ni.2022-211964
Luo YL, Li MX, Cheng Q, et al. Case-control Study on Risk Factors of Perianal Infection in Patients with Hematological Malignancy undergoing Chemotherapy. J Nurs. 2022; 29(7): 7-11. https://doi.org/10.16460/j.issn1008-9969.2022.07.007
Kotloff K, Nataro JP, Blackwelder WC, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013; 382(9888): 209-222. https://doi.org/10.1016/s0140-6736(13)60844-2
Association. HBOCMD, Association. HBOCM. Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (revised in 2022). Chinese Journal of Internal Medicine. 61(5): 480-487.
Diagnostic Criteria for Infectious Diarrhea [EB/OL].
Group ECO (2012) Physical state score (ECOG scoring). Chin Arch General Surg (Electronic Edition). 2022; 6(6): 556.
Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019; 25(4): 625-638. https://doi.org/10.1016/j.bbmt.2018.12.758.
Ministry of Health of the PRC. Diagnostic criteria for infectious diarrhea (WS 271-2007). http://std.samr.gov.cn/hb/search
Fan XJ, Shi ZT, Sun X. Effect Analysis of Chinese Medicine Combined with Cisplatin on Tumor Related Index, Karnofsky Score and Ecog Score in Patients with Rectal Cancer. Chin Arch Tradit Chin Med. 2017; 35(11): 2969-2972. https://doi.org/10.13193/j.issn.1673-7717.2017.11.066
Yu HY. Study on TCM Syndromes of Maligant Hematological Disease Chemotherapy-related Diarrhea. http://kns-cnki-net-s.webvpn.njmu.edu.cn:8118/kcms/detail/detail.aspx?dbcode=CMFD&db name=CMFD202201&filename=1021120092.nh&uniplatform=NZKPT&v=eTU_A26r_3phnbQ6kdXwheNEMb9DWGbVejW13NlA1yfoJo_KJFiQuadXjktyhsl (Accessed in January 3, 2022).
Hu XR, Liao QF. Nursing of patients with multiple myeloma receiving bortezomib-based combination therapy. Chin J Nurs. 2008; 11: 1002-1004.
Zhang MQ, Liu KL, Wang YD, Su H, Wu J, Liu H. Multiple myeloma presenting with chronic diarrhea: A case. World Chin J Digestology. 2016; 24(32): 4415-4418. https://doi.org/10.11569/wcjd.v24.i32.4415
Wang H, Han F, Tu YX. Clinical analysis of incidence of diarrhea in ICU patients. Chin J Nosocomiol. 2014; 24(2): 372-373+379. https://doi.org/10.11816/cn.ni.2014-124297
Zeng C, Lu YH, Ma SL, Ying ZT. Managing the Adverse Reactions of Chimeric Antigen Receptor T Cell Therapy for 95 Patients with Relapsed Refractory B-cell Lymphoma. Nurs J Chin People's Liberation Army. 2021; 38(1): 80-83. https://doi.org/10.3969/j.issn.1008-9993.2021.01.021
Luo XQ, Zeng YJ, Zhang C, et al. Clinical study on the chimeric antigen receptor T cells in the treatment of relapsed/refractory acute lymphoblast leukemia. Chin J Blood Transfus. 2016; 29(10): 1096-1098. https://doi.org/10.13303/j.cjbt.issn.1004-549x.2016.10.003
Ye CY, Zhao LN, Wang SY, et al. Analysis of Related Early Warning Indexes of Cytokine Release Syndrome in Multiple Myeloma Patients after CAR-T Treatment. J Exp Hematol. 2021; 29(4): 1203-1208. https://doi.org/10.19746/j.cnki.issn1009-2137.2021.04.028
Terpos E, Katodritou E, De La Rubia J, et al. Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice. Eur J Haematol. 2018; 101(4): 556-565. https://doi.org/10.1111/ejh.13147
Laubach JP, Tuchman SA, Rosenblatt JM, et al. Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma. Blood Cancer J. 2018; 11(2): 20. https://doi.org/10.1038/s41408-021-00407-5
Shi YM, Bai L, Zhou YT, Zhang SX. Research progress on influencing factors of diarrhea in patients during enteral nutrition. Chin Nurs Res. 2017; 31(14): 1673-1676. https://doi.org/10.3969/j.issn.1009-6493.2017.14.003
Guo LT, Sun JJ, Zhang L, Zhu ZJ, Lei JE, Liu Y. Influencing factors for antibiotic-associated diarrhea in critically ill patients. Chin J Nosocomiol. 2019; 29(5): 661-664. https://doi.org/10.11816/cn.ni.2019-180402
Zvolensky M, Jardin C, Farris SG, et al. Gut interpretations: how difficulties in emotion regulation may help explain the relation of visceral sensitivity with depression and anxiety among young adults with gastrointestinal symptoms. Psychol Health Med. 2018; 23(7): 840-845. https://doi.org/10.1080/13548506.2018.1455984

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Risk factors for non-infectious diarrhea of patients with multiple myeloma after chimeric antigen receptor T- cell immunotherapy: A retrospective observational study

Status:

Version 1

Abstract

Aims

Methods

Results

Conclusions

Introduction

Methods

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1