Transplantation of highly purified CD34+Thy-I+ hematopoietic stem cells in patients with recurrent indolent non-hodgkin's lymphoma

Julie Marie Vose, Philip Jay Bierman, James C. Lynch, Kerry Atkinson, Christopher Juttner, Elie Hanania, Robert G Bociek, James Olen Armitage

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL). Patients and methods: Twenty-six patients with recurrent indolent NHL or MCL were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: ≥5 × 105 viable and pure HSC/kg; cohort 2: ≥3 × 105 HSC/kg). Results: We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/μL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/μL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point post-transplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%. Conclusions: CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population.

Original languageEnglish (US)
Pages (from-to)680-687
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume7
Issue number12
DOIs
StatePublished - Jan 1 2001

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Hematopoietic Stem Cells
Non-Hodgkin's Lymphoma
Transplantation
Granulocyte Colony-Stimulating Factor
Cyclophosphamide
Mantle-Cell Lymphoma
Erythrocyte Transfusion
Platelet Transfusion
Lymphoma
Neutrophils
Drug Therapy
Carmustine
Blood Component Removal
Pneumocystis Pneumonia
Respiratory Syncytial Viruses
Cytarabine
Etoposide
Infection
Human Influenza
Disease-Free Survival

Keywords

  • Autologous stem cell transplantation
  • Hematopoietic stem cells
  • High-dose chemotherapy
  • Mantle cell lymphoma
  • Non-Hodgkin's lymphoma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Transplantation of highly purified CD34+Thy-I+ hematopoietic stem cells in patients with recurrent indolent non-hodgkin's lymphoma. / Vose, Julie Marie; Bierman, Philip Jay; Lynch, James C.; Atkinson, Kerry; Juttner, Christopher; Hanania, Elie; Bociek, Robert G; Armitage, James Olen.

In: Biology of Blood and Marrow Transplantation, Vol. 7, No. 12, 01.01.2001, p. 680-687.

Research output: Contribution to journalArticle

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T1 - Transplantation of highly purified CD34+Thy-I+ hematopoietic stem cells in patients with recurrent indolent non-hodgkin's lymphoma

AU - Vose, Julie Marie

AU - Bierman, Philip Jay

AU - Lynch, James C.

AU - Atkinson, Kerry

AU - Juttner, Christopher

AU - Hanania, Elie

AU - Bociek, Robert G

AU - Armitage, James Olen

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N2 - Purpose: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL). Patients and methods: Twenty-six patients with recurrent indolent NHL or MCL were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: ≥5 × 105 viable and pure HSC/kg; cohort 2: ≥3 × 105 HSC/kg). Results: We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/μL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/μL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point post-transplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%. Conclusions: CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population.

AB - Purpose: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL). Patients and methods: Twenty-six patients with recurrent indolent NHL or MCL were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: ≥5 × 105 viable and pure HSC/kg; cohort 2: ≥3 × 105 HSC/kg). Results: We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/μL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/μL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point post-transplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%. Conclusions: CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population.

KW - Autologous stem cell transplantation

KW - Hematopoietic stem cells

KW - High-dose chemotherapy

KW - Mantle cell lymphoma

KW - Non-Hodgkin's lymphoma

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