Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma

Bone Marrow Transplantation volume 45, pages 801–802 (2010)Cite this article

Several different high-dose therapy (HDT) conditioning regimens have been used for non-Hodgkin's lymphoma (NHL), such as BEAM (carmustine, etoposide, cytosine arabinoside, melphalan), BEAC (carmustine, etoposide, cytosine arabinoside, cyclophosphamide), and CBV (cyclophosphamide, carmustine, etoposide). Carmustine is an active drug in the HDT of NHL. Introduction of i.v. BU as an alternative to oral BU rekindled interest in optimizing the conditioning regimen to improve treatment outcome after allogeneic hematopoietic SCT for myelogenous leukemia.1, 2 The use of i.v. BU and CY suggested a lower incidence of serious hepatic veno-occlusive disease (VOD) and other treatment-related serious adverse events compared with what would be expected after oral BU and CY.3 Once-daily i.v. BU is convenient to give, well-tolerated, efficacious and reduced toxicity. The BU, melphalan and thiotepa (BuMelTT) regimen has shown high activity in the treatment of patients with breast cancer, ovarian cancer, aggressive lymphoma and relapsed Hodgkin's disease.4, 5, 6 Given the limited toxicity observed with i.v. BU and the known activity of BuMelTT regimen in NHL, we developed a protocol using once-daily i.v. BU/melphalan/thiotepa regimen as a conditioning for HDT in the patients with high-risk or relapsed NHL.

Between March and December 2008, 13 patients with relapsed or primary refractory NHL but sensitive to salvage chemotherapy or chemo-sensitive high-risk NHL underwent HDT with i.v. BU/melphalan/thiotepa regimen followed by autologous SCT at the Soonchunhyang University Hospital, Asan Medical Center of Ulsan University and Samsung Medical Center of Sungkyunkwan University, Seoul, Korea. The conditioning regimen consisted of BU 130 mg/m2/day i.v. on days −8, −7 and −6, melphalan 50 mg/m2/day i.v. on days −5 and −4 and thiotepa 250 mg/m2/day i.v. on days −3 and −2. One patient did not show recovery in neutrophil and plt counts and the disease relapsed on day 30; another patient died on day 74 due to sepsis without recovery of plts. The remaining patients achieved an ANC>500/mm3 at a median of 10 days (range 9–30) and an unsupported plt count of >20 000/mm3 at a median 20 days (range 11–35) after infusion of PBSC. Grade 3–4 regimen-related toxicities occurred in nine of 13 (69.2%) patients, mainly including mucositis, GI and hepatic toxicity. Six patients (46%) developed hepatic VOD including one severe type and three patients documented infections (klebsiella pneumonia, streptococcal pneumonia and sepsis due to MRSA and CMV bacteremia), one died of sepsis on post-transplant day 74. In all, one patient was not evaluable for response because of septic death. Four (80%) out of five patients with PR state before HDT achieved CR after HDT and one out of seven patients with CR state progressed during HDT; the remaining 10 out of 12 patients achieved or maintained CR after HDT. During the follow-up period (median 312 days, range 74–467), four patients relapsed after CR and EFS was 60, 102, 104 and 203 days, respectively (Table 1).

Table 1 Clinical data of 13 patients undergoing HDT using ivB-MT regimen followed by autologous SCT in the patients with high-risk or relapsed NHL
Full size table

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant 2002; 8: 468–476.

    Article  CAS  PubMed  Google Scholar 

  2. Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M et al. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant 2008; 14: 672–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kashyap A, Wingard J, Cagnoni P, Roy J, Tarantolo S, Hu W et al. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant 2002; 8: 493–500.

    Article  CAS  PubMed  Google Scholar 

  4. Bensinger WI, Schiffman KS, Holmberg L, Appelbaum FR, Maziarz R, Montgomery P et al. High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer. Bone Marrow Transplant 1997; 19: 1183–1189.

    Article  CAS  PubMed  Google Scholar 

  5. Holmberg LA, Demirer T, Rowley S, Buckner CD, Goodman G, Maziarz R et al. High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer. Bone Marrow Transplant 1998; 22: 651–659.

    Article  CAS  PubMed  Google Scholar 

  6. Schiffman K, Buckner CD, Maziarz R, Maloney DG, Appelbaum FR, Press O et al. High-dose busulfan, melphalan, and thiotepa followed by autologous peripheral blood stem cell transplantation in patients with aggressive lymphoma or relapsed Hodgkin's disease. Biol Blood Marrow Transplant 1997; 3: 261–266.

    CAS  PubMed  Google Scholar 

  7. Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB . Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Biol Blood Marrow Transplant 1999; 5: 306–315.

    Article  CAS  PubMed  Google Scholar 

  8. Zaucha R, Gooley T, Holmberg L, Gopal AK, Press O, Maloney D et al. High-dose chemotherapy with BEAM or Busulphan/Melphalan and Thiotepa followed by hematopoietic cell transplantation in malignant lymphoma. Leuk Lymphoma 2008; 49: 1899–1906.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea

    S-C Lee & J-H Won

  2. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    S J Kim & W S Kim

  3. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    D H Lee & C Suh

Authors
  1. S-C Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S J Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D H Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W S Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J-H Won
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J-H Won.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, SC., Kim, S., Lee, D. et al. Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 45, 801–802 (2010). https://doi.org/10.1038/bmt.2009.240

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.240

This article is cited by

Search

Advanced search

Quick links