Effects of cladribine: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major Research Findings

Cladribine is a medication used to treat various diseases, including hairy cell leukemia ( 19 ) and multiple sclerosis ( 3 , 11 , 2 , 1 , 6 , 8 , 7 , 4 , 10 ). Research has shown that cladribine can reduce the number of lymphocytes ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 4 ), induce apoptosis ( 20 , 13 , 17 , 16 ), and inhibit cell growth ( 5 , 14 , 15 , 9 ). Additionally, cladribine can affect the effects of interleukin-1β ( 11 ) and neurofilament light chain ( 2 ). It has also been shown to have synergistic effects when combined with other medications ( 15 , 9 , 12 ).

Benefits and Risks

Benefits Summary

Cladribine has the potential to be effective in treating diseases such as hairy cell leukemia ( 19 ) and multiple sclerosis ( 3 , 11 , 2 , 10 ). It may also exhibit synergistic effects when combined with other medications ( 15 , 9 , 12 ).

Risks Summary

Cladribine may cause side effects such as reducing the number of lymphocytes ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 4 ), inducing apoptosis ( 20 , 13 , 17 , 16 ), and inhibiting cell growth ( 5 , 14 , 15 , 9 ). It may also affect the function of the heart ( 7 ). Furthermore, cladribine can weaken the immune system ( 19 , 3 , 11 , 2 , 1 , 6 , 8 , 4 ), making individuals more susceptible to infections. It is crucial to be aware of these risks before using cladribine.

Comparison Between Studies

Similarities Between Studies

Numerous studies consistently demonstrate that cladribine can reduce the number of lymphocytes ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 4 ), induce apoptosis ( 20 , 13 , 17 , 16 ), and inhibit cell growth ( 5 , 14 , 15 , 9 ). These effects are believed to be based on the pharmacological actions of cladribine.

Differences Between Studies

The effects of cladribine can vary depending on the disease and the method of administration. For instance, in treating multiple sclerosis ( 3 , 11 , 2 , 1 , 6 , 8 , 7 , 4 , 10 ), research has indicated that cladribine can reduce the number of lymphocytes ( 6 , 8 ) and lower neurofilament light chain levels ( 2 ). On the other hand, in treating hairy cell leukemia ( 19 ), cladribine has been shown to cause immunodeficiency ( 19 ) and suppress tumor growth. The method of cladribine administration can also influence its effects. For example, cladribine can be administered through intravenous injections ( 21 ) or orally ( 3 , 11 , 2 , 1 , 6 , 8 , 7 , 4 , 10 ). Different administration methods may result in different effects and side effects of cladribine.

Consistency and Contradictions in the Findings

There is both consistency and contradiction in the research findings regarding the effects of cladribine. For example, many studies demonstrate that cladribine can reduce the number of lymphocytes ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 4 ). However, the duration and extent of this effect can vary across studies. Additionally, although research suggests that cladribine exhibits synergistic effects when combined with other medications ( 15 , 9 , 12 ), the effectiveness of these combinations may depend on the disease and the type of medications involved.

Considerations for Real-World Application

Cladribine is used to treat various diseases, including hairy cell leukemia ( 19 ) and multiple sclerosis ( 3 , 11 , 2 , 10 ). However, it also carries the risk of side effects ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 7 , 4 ). When using cladribine, it is crucial to follow the instructions of a healthcare professional and understand the risks and benefits. Additionally, cladribine can interact with other medications, so it is essential to inform your doctor about any other medications you are taking. Cladribine is used to treat a variety of conditions, including autoimmune diseases ( 3 , 11 , 2 , 1 , 6 , 8 , 7 , 4 , 10 ) and cancers ( 19 , 20 , 14 , 15 , 17 , 16 , 9 , 12 ). Consult with your doctor to determine the appropriate usage for your individual circumstances.

Limitations of Current Research

Research on the effects of cladribine is still insufficient, particularly regarding long-term effects and safety. Additionally, the effectiveness of cladribine can vary from person to person. Therefore, further research is needed to understand the effects and side effects of cladribine.

Future Research Directions

Continued research on the effects of cladribine is necessary. Studies on long-term effects and safety are particularly lacking. Furthermore, research considering individual differences is required as the effectiveness of cladribine can vary among individuals. Additionally, future research on the combined effects of cladribine with other medications is necessary.

Conclusion

Cladribine is a medication used to treat diseases such as hairy cell leukemia ( 19 ) and multiple sclerosis ( 3 , 11 , 2 , 10 ). Cladribine has been shown to have various effects, including reducing the number of lymphocytes ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 4 ), inducing apoptosis ( 20 , 13 , 17 , 16 ), and inhibiting cell growth ( 5 , 14 , 15 , 9 ). However, it is important to use cladribine under the guidance of a doctor, understanding both its benefits and risks ( 20 , 5 , 11 , 2 , 1 , 6 , 8 , 7 , 4 ).

Literature analysis of 23 papers
Positive Content
23
Neutral Content
0
Negative Content
0
Article Type
1
0
0
1
23
1.

Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis.

Author: Holm HansenRikke, von EssenMarina Rode, MahlerMie Reith, CobanovicStefan, BinkoTomas Sorm, SellebjergFinn

Multiple sclerosis treatment
None

Cladribine tablet therapy is an effective treatment for multiple sclerosis (MS), but its mechanism of action on T and B cell subsets remains unclear. This study investigated the effects of cladribine on the peripheral pool of T and B cell subsets and their reactivity towards central nervous system (CNS) antigens.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary.

Author: OhJiwon, WalkerBryan, GiovannoniGavin, JackDominic, DangondFernando, NoltingAxel, AldridgeJulie, LebsonLori A, LeistThomas P

Well-tolerated
Side effects

This study examined the side effects of cladribine tablets, a medication for relapsing forms of multiple sclerosis (MS), in the first 12 weeks of two clinical studies. Cladribine tablets were generally well-tolerated, with most side effects being mild.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
CommentA short article/note that provides an opinion/perspective/interpretation on a published paper/topic.

Language : English

5.

Effects on Melanoma Cell Lines Suggest No Significant Risk of Melanoma Under Cladribine Treatment.

Author: Lebrun-FrenayChristine, BerestjukIlona, CohenMikael, Tartare-DeckertSophie

Melanoma inhibition
Lymphocyte depletion

Cladribine, an oral synthetic purine analog, is effective for treating highly active relapsing-remitting multiple sclerosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Effects of cladribine tablets on heart rate, atrio-ventricular conduction and cardiac repolarization in patients with relapsing multiple sclerosis.

Author: HermannRobert, LitwinJeffrey S, FribergLena E, DangondFernando, MunafoAlain

Relapsing MS treatment
Cardiac repolarization effects
Heart rate effects

Cladribine tablets are effective in treating relapsing multiple sclerosis. This study examines the impact of cladribine on heart rate, AV conduction, and cardiac repolarization in patients with relapsing-remitting multiple sclerosis.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis.

Author: TerranovaNadia, HickingChristine, DangondFernando, MunafoAlain

Multiple sclerosis treatment
Lymphopenia

Cladribine Tablets (MAVENCLAD<sup>&#174;</sup>) selectively reduce absolute lymphocyte counts (ALCs) in patients with multiple sclerosis. Treatment postponements during year 2 have been proposed for patients with a low ALC to manage potential lymphopenia.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Cladribine in combination with entinostat synergistically elicits anti-proliferative/anti-survival effects on multiple myeloma cells.

Author: WangBolun, LyuHui, PeiShanshan, SongDeye, NiJiangdong, LiuBolin

Antitumor activity
MM treatment
Synergistic effects

This study investigated the effectiveness of combining cladribine and entinostat, two drugs used to treat different types of leukemia, to treat multiple myeloma (MM). The researchers found that the combination was more effective than either drug alone in inhibiting MM cell growth and promoting apoptosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study.

Author: ComiGiancarlo, CookStuart, RammohanKottil, Soelberg SorensenPer, VermerschPatrick, AdenijiAbidemi K, DangondFernando, GiovannoniGavin

Clinical improvement
RRMS treatment

Treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This study presented the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis.

Author: MusellaAlessandra, MandolesiGeorgia, GentileAntonietta, RossiSilvia, StuderValeria, MottaCaterina, SepmanHelena, FresegnaDiego, HajiNabila, PaolilloAndrea, MatareseGiuseppe, CentonzeDiego

EAE treatment

Cladribine, administered intracerebroventricularly, reduced clinical deficits and reversed glutamate-mediated synaptic alterations in EAE mice, a model of multiple sclerosis. While it did not affect microglial and astroglial activation, cladribine blocked synaptic alterations by interfering with interleukin-1β effects, demonstrating a neuroprotective action independent of its immunosuppressant effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Effects of 2-chlorodeoxyadenosine (Cladribine) on primary rat microglia.

Author: SinghVikramjeet, VossElke Verena, BénardaisKarelle, StangelMartin

Treat MS
Leukopenia

2-chlorodeoxyadenosine (CdA) induces apoptosis in primary rat microglia, inhibiting their proliferation. The effects are mediated by the mitochondrial apoptotic pathway.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

In vitro and in vivo growth-inhibitory effects of cladribine on neoplastic mast cells exhibiting the imatinib-resistant KIT mutation D816V.

Author: BöhmAlexandra, SonneckKaroline, GleixnerKaroline V, SchuchKarina, PicklWinfried F, BlattKatharina, PeterBarbara, HerrmannHarald, SchernthanerGerit-Holger, PehambergerHubert, RabitschWerner, SperrWolfgang R, ValentPeter

Treatment for advanced SM

Cladribine is a drug that is used to treat certain types of cancer. This study investigated the effects of cladribine on systemic mastocytosis (SM), a disease that causes an overgrowth of mast cells. The study found that cladribine was effective in treating SM.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects.

Author: GleixnerKaroline V, MayerhoferMatthias, AichbergerKarl J, DerdakSophia, SonneckKaroline, BöhmAlexandra, GruzeAlexander, SamorapoompichitPuchit, ManleyPaul W, FabbroDoriano, PicklWinfried F, SillaberChristian, ValentPeter

SM treatment

PKC412 and AMN107, novel TK-targeting drugs, counteract the TK activity of KIT D816V and inhibit the growth of neoplastic mast cells in patients with systemic mastocytosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Cytotoxic effects of cladribine and tezacitabine toward HL-60.

Author: StachnikKrzysztof, GriebPaweł, SkierskiJanusz S

Cell death
Toxicity

Tezacitabine was less toxic than cladribine after 24 hours of exposure, but its toxicity increased significantly after 48 hours, leading to massive cell death at lower doses than cladribine. Further studies on the effects of prolonged exposure on tezacitabine's clinical efficacy are warranted.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Determination of the in vivo effects of cladribine alone and its combination with cyclophosphamide or cyclophosphamide and mitoxantrone on Bax and Bcl-2 protein expression in B-CLL cells.

Author: KobylinskaAgnieszka, BlonskiJerzy Z, HanausekMalgorzata, WalaszekZbigniew, RobakTadeusz, KilianskaZofia M

B-CLL treatment

This study investigates the correlation between expression of Bax and Bcl-2 (Bax/Bcl-2 ratio) in B-CLL cells and the response to chemotherapy. The results suggest that the Bax/Bcl-2 ratio is elevated in patients treated with cladribine combined with mitoxantrone and cyclophosphamide, indicating enhanced apoptosis induction.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

The effects of cladribine and fludarabine on DNA methylation in K562 cells.

Author: WyczechowskaDorota, Fabianowska-MajewskaKrystyna

Antileukemic efficacy

Cladribine and fludarabine, antileukemic drugs, were found to inhibit DNA methylation in a cell line. Both drugs inactivated SAH hydrolase, an enzyme involved in the methylation process. This inhibition of DNA methylation by these drugs could contribute to their antileukemic efficacy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Induction of apoptosis by cladribine (2-CdA), gemcitabine and other chemotherapeutic drugs on CD34+/CD38+ and CD34+/CD38- hematopoietic progenitor cells: selective effects of doxorubicin and 2-CdA with protection of immature cells.

Author: ChowKai U, BoehrerSimone, BojungaJoerg, StielerManuela, RummelMathias J, FauthFlorian, SchneiderBernd, MartinHans, HoelzerDieter, WeidmannEckhart, MitrouParis S

Hematologic disease treatment
Stem cell purging
Stem cell toxicity

This study examines the effects of various chemotherapeutic drugs on the apoptosis of stem cells. Doxorubicin and cladribine selectively induce apoptosis in more mature CD34+/CD38+ stem cells while protecting the less differentiated CD34+/CD38- cells. This suggests that these drugs may be effective and safe alternatives for ex vivo purging of autologous grafts.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.

Author: GriebP, KamienowskiJ, JaniszM, KuśnierczykP, KawiakJ, HoserG, ChrapustaS J

Autoimmune disease treatment
Erythroid toxicity
Myeloid toxicity

This study compares two different regimens of cladribine, a lymphocytotoxic drug used for multiple sclerosis, evaluating their effectiveness and side effects on various blood cell populations.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Differential effects of cladribine and gemcitabine on erythroid and granulocytic progenitors from patients with chronic myeloid leukemia.

Author: SchirmerM, GeisenF, TiefenthalerM, KonwalinkaG

CML cell purging

This study investigated the potential of cladribine and gemcitabine, nucleoside analogs, to selectively eliminate chronic myeloid leukemia (CML) cells from bone marrow. The study found that these drugs were more effective in inhibiting CML cells than normal bone marrow progenitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Comparative effects of cladribine, fludarabine and pentostatin on nucleotide metabolism in T- and B-cell lines.

Author: WilsonP K, SzabadosE, MulliganS P, ChristophersonR I

Lymphoid malignancy treatment

The study compared the effects of cladribine, fludarabine, and pentostatin on nucleotide metabolism in human leukemia and lymphoma cell lines. This may provide insights into the mechanisms of cytotoxicity of these drugs.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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