Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis

Results of a phase II trial

Adam D. Cohen, Ping Zhou, Joanne Chou, Julie Teruya-Feldstein, Lilian Reich, Hani Hassoun, Beth Levine, Daniel A. Filippa, Elyn Riedel, Tarun Kewalramani, Michael D. Stubblefield, Martin Fleisher, Stephen D Nimer, Raymond L. Comenzo

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving ≤2 organ systems were assigned to MEL 100, 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients.

Original languageEnglish
Pages (from-to)224-233
Number of pages10
JournalBritish Journal of Haematology
Volume139
Issue number2
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

Thalidomide
Stem Cell Transplantation
Amyloidosis
Dexamethasone
Light
Stem Cells
Transplants
Melphalan
Mortality
Therapeutics
Kidney
Peripheral Nervous System
Plasma Cells
Venous Thrombosis
Confidence Intervals
Survival
Liver

Keywords

  • Amyloidosis
  • Clinical trials
  • Risk-adapted melphalan
  • Stem cell transplantation
  • Thalidomide

ASJC Scopus subject areas

  • Hematology

Cite this

Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis : Results of a phase II trial. / Cohen, Adam D.; Zhou, Ping; Chou, Joanne; Teruya-Feldstein, Julie; Reich, Lilian; Hassoun, Hani; Levine, Beth; Filippa, Daniel A.; Riedel, Elyn; Kewalramani, Tarun; Stubblefield, Michael D.; Fleisher, Martin; Nimer, Stephen D; Comenzo, Raymond L.

In: British Journal of Haematology, Vol. 139, No. 2, 01.10.2007, p. 224-233.

Research output: Contribution to journalArticle

Cohen, AD, Zhou, P, Chou, J, Teruya-Feldstein, J, Reich, L, Hassoun, H, Levine, B, Filippa, DA, Riedel, E, Kewalramani, T, Stubblefield, MD, Fleisher, M, Nimer, SD & Comenzo, RL 2007, 'Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis: Results of a phase II trial', British Journal of Haematology, vol. 139, no. 2, pp. 224-233. https://doi.org/10.1111/j.1365-2141.2007.06783.x
Cohen, Adam D. ; Zhou, Ping ; Chou, Joanne ; Teruya-Feldstein, Julie ; Reich, Lilian ; Hassoun, Hani ; Levine, Beth ; Filippa, Daniel A. ; Riedel, Elyn ; Kewalramani, Tarun ; Stubblefield, Michael D. ; Fleisher, Martin ; Nimer, Stephen D ; Comenzo, Raymond L. / Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis : Results of a phase II trial. In: British Journal of Haematology. 2007 ; Vol. 139, No. 2. pp. 224-233.
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abstract = "High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving ≤2 organ systems were assigned to MEL 100, 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67{\%}), heart (24{\%}), liver/GI (22{\%}) and peripheral nervous system (18{\%}), with 31{\%} having two organs involved. TRM was 4.4{\%}. Thirty-one patients began adjuvant therapy, with 16 (52{\%}) completing 9 months of treatment and 13 (42{\%}) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71{\%} (36{\%} complete response), with 44{\%} having organ responses. With a median follow-up of 31 months, 2-year survival was 84{\%} (95{\%} confidence interval: 73{\%}, 94{\%}). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients.",
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