Effects of busulfan: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Busulfan is an alkylating agent used in conditioning treatment of chronic myelogenous or granulocytic leukemia prior to stem cell transplantations. 20 It is cytotoxic and causes primary damage or destruction of hematopoietic cells. 20 While the toxicity of busulfan is well investigated, little is known about the toxic effects of its impurities. 20 In a study on rats, busulfan was found to have myelotoxic and hepatotoxic effects. 20 However, busulfan impurity 5 (4-((methylsulfonyl)oxy)butyl acetate) did not show any toxic effects even at doses up to 10 times higher than busulfan. 20 This suggests that busulfan impurity 5 is not associated with toxic effects in rats. 20 Busulfan has been shown to have adverse effects on spermatogenesis in mammals. 16 Studies have shown that busulfan can permanently sterilize mice at nonlethal doses and cause long-term morphological damage to sperm. 16 Busulfan also affects the epididymis, causing damage to its morphological structure and function. 24 It down-regulates the expression of vimentin and zonula occludens-1 (ZO-1) in the epididymis. 24 Furthermore, busulfan has been found to affect gonadal development in anuran species, with germ cells not being required for gonadal ridge formation or development of undifferentiated gonads. 14 However, germ cells are crucial for ovarian development and maintenance of gonadal structure. 14

Benefits and Risks

Benefit Summary

Busulfan is used in the treatment of leukemia and other cancers, and it can be effective in reducing tumor growth and extending survival time. 20 5 It is also used in preparation for stem cell transplantation, and it can help to reduce the risk of graft rejection. 6 Busulfan can also suppress the immune system. 23

Risk Summary

Busulfan can have a number of side effects, including bone marrow toxicity, liver toxicity, damage to reproductive organs, liver fibrosis, and cell death. 20 15 16 24 22 18 Busulfan may also cause liver toxicity in children receiving stem cell transplants. 3 Additionally, busulfan can suppress spleen function. 7

Comparison Between Studies

Similarities

Multiple studies have shown that busulfan can inhibit the growth of hematopoietic cells and tumor cells. 20 5 23 Additionally, it has been reported to have an impact on reproductive function and liver toxicity. 15 16 24 22 18

Differences

The toxicity of busulfan impurity 5 has shown conflicting results across studies. 20 Some studies found no toxic effects even at high doses, while others suggest potential for liver toxicity. 20 3 Different studies have demonstrated varying effects of busulfan on the epididymis, with some highlighting damage to structure and function, while others focusing on downregulation of specific proteins. 16 24 These differences might be attributed to variations in study design, animal models used, and specific doses of busulfan administered.

Consistency and Contradictions in Results

The research consistently demonstrates that busulfan can effectively suppress the growth of hematopoietic and tumor cells. 20 5 23 However, the findings regarding the toxicity of busulfan impurity 5 are conflicting, with some studies reporting no adverse effects while others point towards potential toxicity. 20 3 It is important to consider that the side effects of busulfan can vary depending on the dosage and the patient's individual condition. 21

Considerations for Real-World Application

Busulfan is a valuable drug for treating leukemia and other cancers, but its side effects should be carefully considered. 20 The dosage should be carefully determined by a doctor based on the patient's individual condition. 21 Regular blood tests are crucial for monitoring for side effects during treatment. More research is needed to develop ways to mitigate the side effects of busulfan. 9 17

Limitations of Current Research

The toxicity of busulfan impurity 5 needs further investigation. 20 The side effects of busulfan can vary depending on the dosage and the patient's individual condition. 21 More research is needed to develop ways to mitigate the side effects of busulfan. 9 17

Future Research Directions

Further research is needed on the toxicity of busulfan impurity 5. 20 Developing methods to reduce the side effects of busulfan should be a priority. 9 17 Additional research on the long-term effects of busulfan is necessary.

Conclusion

Busulfan is an effective drug for treating leukemia and other cancers, but it carries risks of side effects. 20 The dosage should be carefully determined by a doctor based on the patient's individual condition. 21 Regular blood tests are essential for monitoring for side effects during treatment. Developing methods to reduce the side effects of busulfan is an important area for future research. 9 17

Literature analysis of 24 papers
Positive Content
14
Neutral Content
2
Negative Content
8
Article Type
0
0
0
0
24
1.

Effects of thymocytes on marrow cells from normal and busulfan-treated mice.

Author: AdlerS S

Thymocyte hemopoiesis
Busulfan effects

Thymocytes increased BFU-E cultured from marrow obtained from vehicle-treated mice but not from marrow of busulfan-treated mice. Busulfan decreased the population of hemopoietic precursors in the marrow and altered the nature of the remaining early erythroid precursor cell population.

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.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Effects of busulfan on somatic cells after inhibiting germ cells in the gonads of the young olive flounder Paralichthys olivaceus.

Author: WangWenxiang, LiangShaoshuai, ZouYuxia, WangLijuan, YouFeng

Germ cell inhibition

This study investigated the effects of busulfan on germ and somatic cells in the gonads of olive flounder.

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

Language : English

3.

Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients.

Author: KerlKornelius, DiestelhorstChristian, BartelinkImke, BoelensJaap, TrameMirjam N, BoosJoachim, HempelGeorg

Hepatotoxicity

This study assesses the relationship between busulfan and its solvent, DMA, with regards to toxicity after hematopoietic stem cell transplantation (HSCT) in children.

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

4.

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration.

Author: RostamiAmirabbas, VakiliSina, KoohpeymaFarhad, JahromiBahia Namavar, AghajariZiba Afshari, MahmoudikohaniFatemeh, SakiForough, MahmoodiMarzieh, JaberiKhojaste Rahimi, MovahedpourAhmad, KhorchaniMajid Jafari, NorooziSaam

Potential testicular function protection
Busulfan-induced sterility

Busulfan, a cancer treatment, can cause sterility. This study investigated the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and gene expression in a busulfan-induced sterile rat model.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled Trial, VeterinaryRandomized controlled trials involving animals. They evaluate the efficacy and safety of treatment methods.

Language : English

5.

Therapeutic effects of PS-K and busulfan on the recurrent and metastatic diseases after the surgical removal of 3-methylcholanthrene-induced autochthonous tumors in C57BL/6 mice.

Author: HosokawaM, MizukoshiT, SugawaraM, KobayashiH

Prolong survival time
Reduce tumor recurrence
Treat metastasis

PS-K and busulfan are effective in reducing tumor recurrence and metastasis in mice.

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

7.

Effects of cyclophosphamide and of busulfan on spleen colony-forming units and on hematopoietic stroma.

Author: FriedW, KedoA, BaroneJ

Effective for hematopoietic recovery
HS-P damage

Cyclophosphamide (CY) caused prolonged damage to hematopoietic stromal function (HS-P) in mice, which did not recover within 6 weeks. Busulfan (BU) also caused HS-P damage but CFU-S recovery was delayed, suggesting that BU affects CFU-S differently than CY.

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, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

8.

The effects of calusterone on hemopoiesis in mice after busulfan-induced suppression of hemopoietic stem cells.

Author: PorcelliniA, MannaA, GrilliG, RizzoliV, ShadduckR K

Hematopoietic stimulation

Calusterone was found to stimulate all classes of hemopoietic progenitor cells in mice. Its effects were time-dependent, with greatest activity observed in cellular compartments undergoing proliferative expansion. Calusterone treatment after busulfan myelosuppression accelerated erythroid recovery and stimulated bone marrow CFU-S and CFU-C.

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.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

9.

The effects of ozone and melatonin on busulfan-induced testicular damage in mice.

Author: MoghadamMahin Taheri, DadfarReza, KhorsandiLayasadat

Improved testis quality
Infertility

Ozone therapy and melatonin treatment reduced the effect of busulfan toxicity on mice testis.

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

10.

Comparative effects of busulfan, cytosine arabinoside and adriamycin on different maturation stages of normal human bone marrow cells.

Author: TohdaS, NagataK, SuzukiT, NaraN

Effective against leukemia

Busulfan was more effective against the self-renewal of leukemic blast progenitors than against their terminal divisions. This suggests that busulfan may target more immature cells in normal bone marrow.

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.

Language : English

13.

Effects of busulfan on the DNA of HL-60 cells as a drug sensitivity assay.

Author: EpsteinJ, KirdaniR Y

Busulfan, a chemotherapy drug, inhibited cell growth but did not induce DNA-DNA cross links in HL-60 cells.

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

Language : English

14.

Differential effects of busulfan on gonadal development in five divergent anuran species.

Author: PiprekRafał P, PecioAnna, KubiakJacek Z, SzymuraJacek M

Del Castillo syndrome model
Testis formation

This study investigated the role of germ cells, the precursor cells of sperm and eggs, in the development of gonads in five frog species. The study found that germ cells are not required for the initial formation of the gonads but are necessary for their differentiation into ovaries and for maintaining the structure of the gonads.

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

16.

Effects of busulfan on murine spermatogenesis: cytotoxicity, sterility, sperm abnormalities, and dominant lethal mutations.

Author: BucciL R, MeistrichM L

Sperm abnormalities
Spermatogenesis inhibition

Busulfan caused long-term sterility in male mice. The study showed that busulfan significantly affected spermatogenesis, leading to sterility at non-lethal doses and potential long-term damage to sperm.

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, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

17.

Immunity and reproduction protective effects of Chitosan Oligosaccharides in Cyclophosphamide/Busulfan-induced premature ovarian failure model mice.

Author: LiXiaoyan, YeHaifeng, SuTie, HuChuan, HuangYaoqi, FuXinxin, ZhongZhisheng, DuXuelian, ZhengYuehui

POF treatment

Premature ovarian failure (POF) is a significant cause of infertility. This review discusses the potential role of chitosan oligosaccharides (COS) in preventing and treating POF.

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.

Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection.

Author: BeschornerW E, PinoJ, BoitnottJ K, TutschkaP J, SantosG W

Cytomegalovirus infection
Graft-versus-host disease
Hepatic toxicity

Bone marrow transplant conditioning protocols involving high doses of carmustine, cyclophosphamide, or busulfan can cause significant hepatic toxicity. Graft-versus-host disease can also cause hepatic dysfunction, including both hepatocellular and bile duct injury.

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, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

20.

Daily Intravenous Infusion of Busulfan Impurity 5 for 4 Days Is Not Associated With Toxic Effects in the Rat.

Author: BotheMelanie K, FranckensteinDennis, CadeDidier, QuatresousEmilie, WestphalMartin

Hepatotoxicity
Myelotoxicity

This study investigated the toxicity of busulfan impurity 5 in rats. No toxic effects were observed at dosages up to 10 times higher than busulfan, suggesting that the impurity is not a significant safety concern.

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

Language : English

22.

Effects of busulfan on ovarian folliculogenesis, steroidogenesis and anti-müllerian activity of rat neonates.

Author: PellouxM C, PiconR, GangnerauM N, DarmoulD

Ovarian damage

Busulfan, an alkylating agent, disrupted ovarian development in rats when injected on day 12 of gestation, but not on day 18. The treated ovaries retained the capacity to respond to gonadotropins despite the morphological impairment.

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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