Treosulfan

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Treosulfan
Treosulfan.svg
Clinical data
Trade names Trecondi, Ovastat
Other names1,2,3,4-Butanetetrol, 1,4-dimethanesulfonate, Threitol 1,4-dimethanesulfonate, Threitol 1,4-bismethanesulfonate; L-Threitol 1,4-bis(methanesulfonate); Threosulphan; Treosulphan; Tresulfan
AHFS/Drugs.com International Drug Names
Pregnancy
category
Routes of
administration
By mouth, intravenous
ATC code
Legal status
Legal status
Identifiers
  • (2S,3S)-2,3-Dihydroxybutane-1,4-diyl dimethanesulfonate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard 100.005.529 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C6H14O8S2
Molar mass 278.29 g·mol−1
3D model (JSmol)
Melting point 101.5 to 105 °C (214.7 to 221.0 °F)
  • CS(=O)(=O)OC[C@@H]([C@H](COS(=O)(=O)C)O)O
  • InChI=1S/C6H14O8S2/c1-15(9,10)13-3-5(7)6(8)4-14-16(2,11)12/h5-8H,3-4H2,1-2H3/t5-,6-/m0/s1
  • Key:YCPOZVAOBBQLRI-WDSKDSINSA-N
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Treosulfan, sold under the brand name Trecondi, is a medication given to people before they have a bone marrow transplant from a donor known as allogeneic hematopoietic stem cell transplantation. It is used as a 'conditioning' treatment to clear the bone marrow and make room for the transplanted bone marrow cells, which can then produce healthy blood cells. [8] [9] It is used together with another medicine called fludarabine in adults and children from one month of age with blood cancers as well as in adults with other severe disorders requiring a bone marrow transplant. [8]

Contents

It belongs to the family of drugs called alkylating agents. [8] In the body, treosulfan is converted into other compounds called epoxides which kill cells, especially cells that develop rapidly such as bone marrow cells, by attaching to their DNA while they are dividing. [8]

The most common side effects in adults and children are infections, nausea (feeling sick), stomatitis (inflammation of the lining of the mouth), vomiting, diarrhoea and abdominal pain (belly ache). [8] Tiredness, febrile neutropenia (low white blood cell counts with fever) and high blood levels of bilirubin (a breakdown product of red blood cells) are also seen in more than 1 in 10 adults, and rash also affects more than 1 in 10 children. [8]

Medical Uses

Treosulfan in combination with fludarabine is indicated as part of conditioning treatment prior to allogeneic haematopoietic stem cell transplantation (alloHSCT) in adults with malignant and non malignant diseases, and in children older than one month with malignant diseases. [8]

History

Treosulfan was approved for use in the European Union in June 2019. [8]

Two main studies showed that treosulfan is at least as effective as busulfan, another medicine used to prepare patients for haematopoietic stem cell transplantation. [8]

In one of the studies, involving 570 adults with acute myeloid leukaemia (a blood cancer) or myelodysplastic syndromes (conditions in which large numbers of abnormal blood cells are produced), 64% of patients given treosulfan (with fludarabine) had a successful transplant and were alive and disease-free after 2 years, compared with 51% of patients given busulfan (with fludarabine). [8]

In an additional study in 70 children with blood cancers, 99% of children given treosulfan (with fludarabine) were alive 3 months after their transplant. [8]

On 23 February 2004, orphan designation (EU/3/04/186) was granted by the European Commission to medac Gesellschaft fuer klinische Spezialpräparate mbH, Germany, for treosulfan for the conditioning treatment prior to haematopoietic progenitor cell transplantation. [10]

Related Research Articles

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce additional normal blood cells. HSCT may be autologous, syngeneic, or allogeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

<span class="mw-page-title-main">Melphalan</span> Chemical compound

Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocarcinoma; and uveal melanoma. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Alemtuzumab</span> Medication

Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis. In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment. It is given by injection into a vein.

Total body irradiation (TBI) is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of radiation-induced lung injury. Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune system, preventing immunologic rejection of transplanted donor bone marrow or blood stem cells. Additionally, high doses of total body irradiation can eradicate residual cancer cells in the transplant recipient, increasing the likelihood that the transplant will be successful.

<span class="mw-page-title-main">Extramedullary hematopoiesis</span> Medical condition

Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.

<span class="mw-page-title-main">Thiotepa</span> Chemical compound

Thiotepa (INN), sold under the brand name Tepadina among others, is an anti-cancer medication.

Defibrotide, sold under the brand name Defitelio, is a mixture of single-stranded oligonucleotides that is purified from the intestinal mucosa of pigs. It is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant, with different limitations in the US and the European Union. It works by protecting the cells lining blood vessels in the liver and preventing blood clotting; the way it does this is not well understood.

Hepatosplenic T-cell lymphoma is a rare form of lymphoma that is generally incurable, except in the case of an allogeneic stem cell transplant. It is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show significant sinusoidal infiltration in the liver, spleen, and bone marrow.

Juvenile myelomonocytic leukemia (JMML) is a rare form of chronic leukemia that affects children, commonly those aged four and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is two (2) years old. The World Health Organization has included JMML as a subcategory of myelodysplastic and myeloproliferative disorders.

<span class="mw-page-title-main">Peripheral stem cell transplantation</span> Method of replacing blood-forming stem cells

Peripheral blood stem cell transplantation (PBSCT), also called "Peripheral stem cell support", is a method of replacing blood-forming stem cells. Stem cells can be destroyed through cancer treatments such as chemotherapy or radiation, as well as any blood-related diseases, such as leukemia, lymphoma, neuroblastoma and multiple myeloma. PBSCT is now a much more common procedure than its bone marrow harvest equivalent due to the ease and less invasive nature of the procedure. Studies suggest that PBSCT has a better outcome in terms of the number of hematopoietic stem cell yield.

<span class="mw-page-title-main">Maribavir</span> Antiviral drug

Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus (CMV). Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.

Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the body's tissue. White blood cells fight off infections that enter the body. Bone marrow progenitor cells known as megakaryocytes produce platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs.

<span class="mw-page-title-main">Haematopoietic system</span>

The haematopoietic system is the system in the body involved in the creation of the cells of blood.

FLAG is a chemotherapy regimen used for relapsed and refractory acute myeloid leukemia (AML). The acronym incorporates the three primary ingredients of the regimen:

  1. Fludarabine: an antimetabolite that, while not active toward AML, increases formation of an active cytarabine metabolite, ara-CTP, in AML cells;
  2. Arabinofuranosyl cytidine : an antimetabolite that has been proven to be the most active toward AML among various cytotoxic drugs in single-drug trials; and
  3. Granulocyte colony-stimulating factor (G-CSF): a glycoprotein that shortens the duration and severity of neutropenia.

Guo Mei is a hematologist and associate director of 307th Hospital of Chinese People’s Liberation Army and deputy director of Radiation Research Institute.

<span class="mw-page-title-main">Shimon Slavin</span> Israeli professor of medicine

Shimon Slavin is an Israeli professor of medicine. He pioneered immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation to cure hematological malignancies and solid tumors. He also used hematopoietic stem cells to induce transplantation tolerance to bone marrow and organ allografts.

<span class="mw-page-title-main">Nirali N. Shah</span> American physician-scientist and pediatric hematologist-oncologist

Nirali N. Shah is an American physician-scientist and pediatric hematologist-oncologist, serving as head of the hematologic malignancies section of the pediatric oncology branch at the National Cancer Institute. She researches the translation of immunotherapeutic approaches to treat high-risk hematologic malignancies in children, adolescents and young adults.

References

  1. 1 2 Trecondi Archived 9 June 2023 at the Wayback Machine Department of Health and Aged Care
  2. "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 21 December 2022. Archived from the original on 3 April 2022. Retrieved 2 January 2023.
  3. TRECONDI (Link Medical Products Pty Ltd T/A Link Pharmaceuticals) Archived 12 October 2022 at the Wayback Machine Department of Health and Aged Care
  4. https://www.tga.gov.au/resources/auspar/auspar-trecondi [ bare URL ]
  5. "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  6. "Treosulfan 5g Powder for Solution for Infusion - Summary of Product Characteristics (SmPC)". (emc). Archived from the original on 20 May 2022. Retrieved 21 April 2020.
  7. "Trecondi Product Information" (PDF). European Medicines Agency (EMA). 21 April 2020.
  8. 1 2 3 4 5 6 7 8 9 10 11 "Trecondi EPAR". European Medicines Agency (EMA). 11 December 2018. Archived from the original on 16 March 2023. Retrieved 21 April 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. Romański M, Wachowiak J, Główka FK (October 2018). "Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives". Clinical Pharmacokinetics. 57 (10): 1255–1265. doi:10.1007/s40262-018-0647-4. PMC   6132445 . PMID   29557088.
  10. "EU/3/04/186". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 16 October 2019. Retrieved 21 April 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .