Efficacy and toxicity of 2-chlorodeoxyadenosine (cladribine)—2h infusion for 5 days—as first-line treatment for advanced low grade non-Hodgkin’s lymphoma

Fridrik, Michael A.; Jäger, Gerald; Kienzer, H.; Hausmaninger, H.; Oppitz, Paulo Petry; Krieger, O.; Zabernigg, August; Lang, Alois; Neubauer, Marcus A.; Weidinger, Gerhard; Schiller, Lothar; Seewann, H. L.; Chott, Andreas; Linkesch, Werner

doi:10.1016/s0959-8049(98)00140-3

Cited by 23 publications

(18 citation statements)

References 20 publications

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“…[4][5][6][7][8][9] A 40% CR rate is within the range of the observed 95% CI (CR rate, 31.6%; 95% CI, 17.5-48.7), and the difference between 31.6% and 40% is not statistically significant in a trial of this size (P ¼ .14). Future approaches to improving the CR rate and remission duration with front-line 2-CdA therapy may involve combination therapy with other chemotherapeutic agents.…”

Section: Discussionsupporting

confidence: 51%

“…[4][5][6][7][8][9] These results also compare favorably with front-line fludarabine in indolent NHL, in which OR rates from 62% to 84% and CR rates from 15% to 47% have been reported. [33][34][35][36][37] Although the median remission duration in this trial was only 1.9 years, 6 patients have ongoing responses that range from 5.9 years to 11 years.…”

Section: Discussionmentioning

confidence: 60%

“…2-Chlorodeoxyadenosine (2-CdA) (cladribine, Leustatin) is a deoxyadenosine purine nucleoside analog that is toxic to both proliferating and resting lymphocytes (for review, see Tallman and Hakimian 1 ), with activity in chronic lymphocytic leukemia (CLL), 2,3 lowgrade NHL, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] and hairy cell leukemia (HCL). [18][19][20][21][22] Initial trials with 2-CdA established a maximal tolerated dose of 0.1 mg/kg per day as a continuous intravenous infusion over 7 days 23 ; however, because of its long half-life, bolus, subcutaneous, and oral regimens have been equally effective.…”

Section: Conclusion 2-mentioning

confidence: 99%

“…[18][19][20][21][22] Initial trials with 2-CdA established a maximal tolerated dose of 0.1 mg/kg per day as a continuous intravenous infusion over 7 days 23 ; however, because of its long half-life, bolus, subcutaneous, and oral regimens have been equally effective. 7,8,12,13,[15][16][17][24][25][26][27] Reported toxicities consist primarily of myelosuppression and bacterial and opportunistic infections, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] with less frequent occurrences of autoimmune hemolytic anemia 28 and neurotoxicity. 29 Rare reports of an increased incidence of second malignancies or transformation to aggressive NHL have not been confirmed.…”

Section: Conclusion 2-mentioning

confidence: 99%

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Prolonged follow‐up after initial therapy with 2‐chlorodeoxyadenosine in patients with indolent non‐Hodgkin lymphoma

Blum¹,

Johnson²,

Niedzwiecki³

et al. 2006

Cancer

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A H2O/dimethyl sulfoxide(DMSO) mixture was used as the coagulation bath for the wet‐spun process of acrylonitrile/ammonium itaconate copolymers fibers. Diffusion coefficient of DMSO in the protofibers prepared by acrylonitrile/ammonium itaconate copolymers was determined. It has been found that diffusion coefficient of DMSO outflow of the protofibers prepared by acrylonitrile/ammonium itaconate copolymers synthesized by the solution polymerization is highest compared with those of acrylonitrile/ammonium itaconate copolymers synthesized by H2O/DMSO mixture suspension polymerization and the aqueous suspension polymerization. With an increase of copolymer concentration in the dope, diffusion coefficient of DMSO decreases continuously. Diffusion coefficient of DMSO increases along with the bath temperature, but the changes of diffusion coefficient values are less prominent as temperature goes beyond 60°C. When DMSO concentration in the coagulation bath was 55 wt %, the value of the diffusion coefficient of DMSO was minimal. Diffusion coefficient of H2O increases with the jet stretch minus ratio increasing. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4447–4451, 2006

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 60%

Section: Conclusion 2-mentioning

confidence: 99%

Section: Conclusion 2-mentioning

confidence: 99%

See 2 more Smart Citations

Prolonged follow‐up after initial therapy with 2‐chlorodeoxyadenosine in patients with indolent non‐Hodgkin lymphoma

Blum¹,

Johnson²,

Niedzwiecki³

et al. 2006

Cancer

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“…[1][2][3][4][5][6][7][8][9][10][11] However, the mechanism of 2CdA-induced cytotoxity remains unclear. In our previous study, treatment with 2CdA was found to induce DNA double-strand breaks, inhibition of DNA repair and cell death in Chinese hamster V79 cells.…”

Section: Introductionmentioning

confidence: 99%

2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

et al. 2000

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The mechanism of apoptosis induced by 2-chloro-2Ј-deoxyadenosine (2CdA) in human leukemia cell line MOLT-4 was investigated. 2CdA induced increases of 3Ј-OH ends of genomic DNA, ladder-like DNA fragmentation and phosphatidylserine translocation to the outer membrane, which are apoptotic characteristics. These apoptotic phenomena induced by 2CdA were inhibited by cycloheximide (CHX; a protein synthesis inhibitor), deoxycytidine (dC; a substrate of deoxycytidine kinase), acetyl Ile-Glu-Thr-Asp aldehyde (Ac-IETD-CHO; a caspase-8 inhibitor) and acetyl Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO; a caspase-3 inhibitor). The protein synthesisdependent expression of Fas and Fas ligand (Fas-L) was detected by treatment with 2CdA. The proteolytic processing of procaspases-8 and -3 to produce active fragments, caspases-8 (p18) and -3 (p17), respectively, was observed after treatment with 2CdA, and suppressed by cycloheximide. Increases in the activities of caspases-8 and -3 were observed after 2CdA treatment. Their activation was also dependent on protein synthesis. These results indicated that 2CdA-induced apoptosis was triggered by phosphorylation of 2CdA followed by the protein synthesis-dependent expression of Fas and Fas-L and activation of caspases-8 and -3. Leukemia (2000) 14, 299-306.

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Synthesis and Functional Investigations of Computer Designed Novel Cladribine‐Like Compounds for the Treatment of Multiple Sclerosis

Yavuz

Çetin

Akdemir

et al. 2017

Archiv der Pharmazie

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Cladribine (2-CdA) is used as an anti-cancer drug but is currently studied as a potential treatment for use in relapsing-remitting multiple sclerosis (MS). In this study, we computer designed, synthesized, and characterized two novel derivatives of 2-CdA, K1-5d and K2-4c, and investigated their underlying mechanism of beneficial effect using the CCRF-CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair-related gene expression profiles using custom arrays along with 2-CdA treatment at non-toxic doses. Then, we determined whether cells underwent apoptosis after treatment with 2-CdA, K1-5d, and K2-4c in CCRF-CEM and RAJI cells, using the DNA fragmentation assay. It was found that both derivatives modulated the expression of the pathway-related genes that are important in inflammatory signaling, apoptosis, ATM/ATR, double-strand break repair, and the cell cycle. Furthermore, 2-CdA, K1-5d, and K2-4c significantly activated apoptosis in both cell lines. In summary, our data demonstrate that although both derivatives act as anti-inflammatory and apoptotic agents, inducing the accumulation of DNA strand breaks and activating the ultimate tumor suppressor p53 in T and B lymphocytes, the K1-5d derivative has shown more promising activities for further studies.

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Efficacy and toxicity of 2-chlorodeoxyadenosine (cladribine)—2h infusion for 5 days—as first-line treatment for advanced low grade non-Hodgkin’s lymphoma

Cited by 23 publications

References 20 publications

Prolonged follow‐up after initial therapy with 2‐chlorodeoxyadenosine in patients with indolent non‐Hodgkin lymphoma

Prolonged follow‐up after initial therapy with 2‐chlorodeoxyadenosine in patients with indolent non‐Hodgkin lymphoma

2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

Synthesis and Functional Investigations of Computer Designed Novel Cladribine‐Like Compounds for the Treatment of Multiple Sclerosis

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