Is high-dose chemotherapy with peripheral stem cell rescue a suitable option for elderly patients affected by aggressive non-Hodgkin's lymphoma?
Authors: D. Bernardi, M. Michieli, M. Rupolo, M. Mazzucato, M. Spina, A. Giacalone, U. Tirelli
Journal: Annals of Oncology (2005)

Elderly patients are usually excluded from high-dose chemotherapy (HDCT) programs, owing to issues concerning the fact that stem cell collection from older patients might have compromised replicative capacity, with a reduced response to hematopoietic growth factors, and that elderly patients may not tolerate intensive chemotherapy [1.Leger C.S. Bredeson C. Kearns B. et al.Autologous blood and marrow transplantation in patients 60 years and older.Biol Blood Marrow Transplant. 2000; 6: 204-210Abstract Full Text PDF PubMed Scopus (29) Google Scholar]. Recent studies, however, show that age is not an obstacle for the collection of a stem cell product, which is capable of restoring normal hematopoietic function [2.Berkahn L. Keating A. Hematopoiesis in the elderly.Hematology. 2004; 9: 159-163Crossref PubMed Scopus (27) Google Scholar].In January 2002, a 70-year-old male patient presented at our institution with stage IVA diffuse large-cell B non-Hodgkin's lymphoma (NHL). An active hepatitis C was present. He was administered six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by radiotherapy on latero-cervical lymph nodes. The patient remained in complete remission (CR) for 2 months, at which time relapse on abdominal lymph nodes and liver was documented. The patient therefore underwent four cycles of rituximab-ESHAP (etoposide, cisplatin, cytarabine, methylprednisolone) followed by a peripheral blood stem cell (PBSC) collection and two subsequent cycles of rituximab-DHAOX (dexamethasone, cytarabine, oxaliplatin) with an additional PBSC collection. In February 2003, the patient underwent HDCT with BEAM (BCNU, etoposide, cytarabine, melphalan) and PBSC reinfusion. At that time, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scores were 6 and 8, respectively, Geriatric Depression Scale (GDS) score was 0 and Mini-Mental State Examination (MMSE) score was 29; aspartate aminotransferase and alanine aminotransferase were 97 and 166 U/l, respectively; and HCV-RNA was 975 495 copies/ml. The partial remission pre-BEAM was converted into a CR after HDCT. Hematopoietic recovery after BEAM occurred on day +9 for neutrophils and day +20 for platelets. No major non-hematological toxicity occurred. The ADL, IADL, GDS and MMSE scores did not show any change after HDCT. Transaminase levels and HCV viremia were boosted immediately after BEAM and dropped to the previous levels thereafter. Eighteen months after HDCT the patient is still in CR and doing well.We think that HDCT with PBSC rescue can be a suitable option for elderly patients affected by aggressive NHL in first relapse [3.Magagnoli M. Castagna L. Timofeeva I. et al.High-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly versus younger lymphoma patients: a matched analysis.Leuk Lymphoma. 2003; 44: 1439-1440Crossref PubMed Scopus (5) Google Scholar]. However, a Complete Geriatric Assessment (CGA) should be performed [4.Balducci L. Extermann M. Management of cancer in the older person: a practical approach.Oncologist. 2000; 5: 224-237Crossref PubMed Scopus (759) Google Scholar]. Similar to what we have already described for elderly patients undergoing first-line treatment for aggressive NHL [5.Bernardi D. Milan I. Balzarotti M. et al.Comprehensive geriatric evaluation in elderly patients with lymphoma: feasibility of a patient-tailored treatment plan.J Clin Oncol. 2003; 21: 754Crossref PubMed Scopus (29) Google Scholar], we designed a CGA-driven approach for elderly patients (between 65 and 75 years of age) with aggressive NHL in first relapse. Patients are stratified into three groups: (i) ‘frail patients’, who do not undergo HDCT; (ii) patients ‘at standard risk’, who scored 6 and 8 in ADL and IADL, respectively, with a GDS score <11 and an MMSE score >21, with a good respiratory function and no grade 2 comorbidities, who undergo HDCT with BEAM; and (iii) patients ‘at intermediate risk’, who scored at least 5 and 7 in ADL and IADL, respectively, with a GDS score <11 and an MMSE score >21 and a score of no more than 2 in one to three comorbidities, who undergo less aggressive HDCT with melphalan.Stratification of patients into different prognostic groups according to a CGA can render HDCT a feasible and, possibly, effective procedure in selected elderly patients affected by aggressive NHL. Elderly patients are usually excluded from high-dose chemotherapy (HDCT) programs, owing to issues concerning the fact that stem cell collection from older patients might have compromised replicative capacity, with a reduced response to hematopoietic growth factors, and that elderly patients may not tolerate intensive chemotherapy [1.Leger C.S. Bredeson C. Kearns B. et al.Autologous blood and marrow transplantation in patients 60 years and older.Biol Blood Marrow Transplant. 2000; 6: 204-210Abstract Full Text PDF PubMed Scopus (29) Google Scholar]. Recent studies, however, show that age is not an obstacle for the collection of a stem cell product, which is capable of restoring normal hematopoietic function [2.Berkahn L. Keating A. Hematopoiesis in the elderly.Hematology. 2004; 9: 159-163Crossref PubMed Scopus (27) Google Scholar]. In January 2002, a 70-year-old male patient presented at our institution with stage IVA diffuse large-cell B non-Hodgkin's lymphoma (NHL). An active hepatitis C was present. He was administered six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by radiotherapy on latero-cervical lymph nodes. The patient remained in complete remission (CR) for 2 months, at which time relapse on abdominal lymph nodes and liver was documented. The patient therefore underwent four cycles of rituximab-ESHAP (etoposide, cisplatin, cytarabine, methylprednisolone) followed by a peripheral blood stem cell (PBSC) collection and two subsequent cycles of rituximab-DHAOX (dexamethasone, cytarabine, oxaliplatin) with an additional PBSC collection. In February 2003, the patient underwent HDCT with BEAM (BCNU, etoposide, cytarabine, melphalan) and PBSC reinfusion. At that time, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scores were 6 and 8, respectively, Geriatric Depression Scale (GDS) score was 0 and Mini-Mental State Examination (MMSE) score was 29; aspartate aminotransferase and alanine aminotransferase were 97 and 166 U/l, respectively; and HCV-RNA was 975 495 copies/ml. The partial remission pre-BEAM was converted into a CR after HDCT. Hematopoietic recovery after BEAM occurred on day +9 for neutrophils and day +20 for platelets. No major non-hematological toxicity occurred. The ADL, IADL, GDS and MMSE scores did not show any change after HDCT. Transaminase levels and HCV viremia were boosted immediately after BEAM and dropped to the previous levels thereafter. Eighteen months after HDCT the patient is still in CR and doing well. We think that HDCT with PBSC rescue can be a suitable option for elderly patients affected by aggressive NHL in first relapse [3.Magagnoli M. Castagna L. Timofeeva I. et al.High-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly versus younger lymphoma patients: a matched analysis.Leuk Lymphoma. 2003; 44: 1439-1440Crossref PubMed Scopus (5) Google Scholar]. However, a Complete Geriatric Assessment (CGA) should be performed [4.Balducci L. Extermann M. Management of cancer in the older person: a practical approach.Oncologist. 2000; 5: 224-237Crossref PubMed Scopus (759) Google Scholar]. Similar to what we have already described for elderly patients undergoing first-line treatment for aggressive NHL [5.Bernardi D. Milan I. Balzarotti M. et al.Comprehensive geriatric evaluation in elderly patients with lymphoma: feasibility of a patient-tailored treatment plan.J Clin Oncol. 2003; 21: 754Crossref PubMed Scopus (29) Google Scholar], we designed a CGA-driven approach for elderly patients (between 65 and 75 years of age) with aggressive NHL in first relapse. Patients are stratified into three groups: (i) ‘frail patients’, who do not undergo HDCT; (ii) patients ‘at standard risk’, who scored 6 and 8 in ADL and IADL, respectively, with a GDS score <11 and an MMSE score >21, with a good respiratory function and no grade 2 comorbidities, who undergo HDCT with BEAM; and (iii) patients ‘at intermediate risk’, who scored at least 5 and 7 in ADL and IADL, respectively, with a GDS score <11 and an MMSE score >21 and a score of no more than 2 in one to three comorbidities, who undergo less aggressive HDCT with melphalan. Stratification of patients into different prognostic groups according to a CGA can render HDCT a feasible and, possibly, effective procedure in selected elderly patients affected by aggressive NHL. This work was supported by ISS and AIRC grants.