Clinical effects of a single dose of cannabinoids to patients with chronic lymphocytic leukemia

被引：7

作者：

Melen, Christopher M. ^{[1
,2
]}

Merrien, Magali ^{[3
]}

Wasik, Agata M. ^{[3
]}

Panagiotidis, Georgios ^{[4
,5
]}

Beck, Olof ^{[4
,5
]}

Sonnevi, Kristina ^{[1
,2
]}

Junlen, Henna-Riikka ^{[1
,2
]}

Christensson, Birger ^{[3
,6
]}

Sander, Birgitta ^{[3
,6
]}

Wahlin, Bjorn Engelbrekt ^{[1
,2
]}

机构：

[1] Karolinska Inst, Dept Med Huddinge, Div Hematol, Stockholm, Sweden

[2] Karolinska Univ Hosp, Med Unit Hematol, Stockholm, Sweden

[3] Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden

[4] Karolinska Inst, Dept Lab Med, Div Pharmacol, Stockholm, Sweden

[5] Univ Hosp, Unit Clin Pharmacol, Stockholm, Sweden

[6] Karolinska Univ Hosp, Dept Clin Pathol & Cytol, Stockholm, Sweden

来源：

LEUKEMIA & LYMPHOMA | 2022年 / 63卷 / 06期

基金：

瑞典研究理事会;

关键词：

Chronic lymphocytic leukemia; lymphoma; cannabinoids; diurnal rhythm; CXCR4; THC; CBD; RECEPTOR; 2; B-CELLS; DIFFERENTIAL EXPRESSION; GROWTH-INHIBITION; MARGINAL ZONE; CANNABIDIOL; CXCR4; CORTISOL; CB1; DELTA(9)-TETRAHYDROCANNABINOL;

D O I：

10.1080/10428194.2021.2020776

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This phase II clinical trial investigates a one-time oromucosal dose of tetrahydrocannabinol/cannabidiol (THC/CBD) in 23 patients with indolent leukemic B cell lymphomas. Primary endpoint was a significant reduction in leukemic B cells. Grade 1 - 2 adverse events were seen in 91% of the patients; most common were dry mouth (78%), vertigo (70%), and somnolence (43%). After THC/CBD a significant reduction in leukemic B cells (median, 11%) occurred within two hours (p = .014), and remained for 6 h without induction of apoptosis or proliferation. Normal B cells and T cells were also reduced. CXCR4 expression increased on leukemic cells and T cells. All effects were gone by 24 h. Our results show that a single dose of THC/CBD affects a wide variety of leukocytes and only transiently reduce malignant cells in blood. Based on this study, THC/CBD shows no therapeutic potential for indolent B cell lymphomas (EudraCT trial no. 2014-005553-39).

引用

页码：1387 / 1397

页数：11

共 45 条

[1] Follicular lymphoma: Update on management and emerging therapies at the dawn of the new decade [J].

Apostolidis, John ;

Mokhtar, Nihad ;

Al Omari, Rawan ;

Darweesh, Mohammed ;

Al Hashmi, Hani .

HEMATOLOGICAL ONCOLOGY, 2020, 38 (03) :213-221

[2] Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome [J].

Bar-Sela, Gil ;

Cohen, Idan ;

Campisi-Pinto, Salvatore ;

Lewitus, Gil M. ;

Oz-Ari, Lanuel ;

Jehassi, Ayellet ;

Peer, Avivit ;

Turgeman, Ilit ;

Vernicova, Olga ;

Berman, Paula ;

Wollner, Mira ;

Moskovitz, Mor ;

Meiri, David .

CANCERS, 2020, 12 (09) :1-18

[3] Cannabinoid Receptor 2 Is Critical for the Homing and Retention of Marginal Zone B Lineage Cells and for Efficient T-Independent Immune Responses [J].

Basu, Sreemanti ;

Ray, Avijit ;

Dittel, Bonnie N. .

JOURNAL OF IMMUNOLOGY, 2011, 187 (11) :5720-5732

[4] Detection of drugs of abuse in exhaled breath using a device for rapid collection: comparison with plasma, urine and self-reporting in 47 drug users [J].

Beck, Olof ;

Stephanson, Niclas ;

Sandqvist, Soren ;

Franck, Johan .

JOURNAL OF BREATH RESEARCH, 2013, 7 (02)

[5] Cortisol increases CXCR4 expression but does not affect CD62L and CCR7 levels on specific T cell subsets in humans [J].

Besedovsky, Luciana ;

Linz, Barbara ;

Dimitrov, Stoyan ;

Groch, Sabine ;

Born, Jan ;

Lange, Tanja .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2014, 306 (11) :E1322-E1329

[6] Cannabinoid Receptor Type 1-and 2-mediated Increase in Cyclic AMP Inhibits T Cell Receptor-triggered Signaling [J].

Boerner, Christine ;

Smida, Michal ;

Hoellt, Volker ;

Schraven, Burkhart ;

Kraus, Juergen .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (51) :35450-35460

[7] Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells [J].

Burger, JA ;

Burger, M ;

Kipps, TJ .

BLOOD, 1999, 94 (11) :3658-3667

[8] The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: Insight into disease biology and new targeted therapies [J].

Burger, Jan A. ;

Gribben, John G. .

SEMINARS IN CANCER BIOLOGY, 2014, 24 :71-81

[9] Cannabinoid Receptors CB1 and CB2 Form Functional Heteromers in Brain [J].

Callen, Lucia ;

Moreno, Estefania ;

Barroso-Chinea, Pedro ;

Moreno-Delgado, David ;

Cortes, Antoni ;

Mallol, Josefa ;

Casado, Vicent ;

Luis Lanciego, Jose ;

Franco, Rafael ;

Lluis, Carmen ;

Canela, Enric I. ;

McCormick, Peter J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (25) :20851-20865

[10] Differential Expression of Intracellular and Extracellular CB2 Cannabinoid Receptor Protein by Human Peripheral Blood Leukocytes [J].

Castaneda, Julie T. ;

Harui, Airi ;

Kiertscher, Sylvia M. ;

Roth, Jeffrey D. ;

Roth, Michael D. .

JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2013, 8 (01) :323-332

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