Feasibility of peripheral blood progenitor cell mobilization and harvest to support chemotherapy intensification in elderly patients with poor prognosis: Non-Hodgkin's lymphoma

Abstract

Mobilized peripheral blood progenitor cells (PBPC) are widely employed in the management of adult patients with high-risk non-Hodgkin's lymphoma (NHL), though their use in the elderly has received little attention. This study was mounted to assess the feasibility of the mobilization, harvesting, and reinfusion of PBPC in NHL patients aged >60. Twenty patients (median age: 67, range: 61-80) with poor-prognosis NHL entered the pilot study: nine others were discarded for various reasons. Thus, the program was applicable to 69% of potential candidates. Fourteen patients were at onset and six were being treated for refractory disease or relapses. Mobilization was induced with cyclophosphamide 4 g/m(2), followed by 5 micro g/kg per day granulocyte-colony stimulating factor (G-CSF) s.c. until PBPC collection or hemopoietic recovery. Sixteen patients (80%) displayed some signs of mobilization (CD34+: >5/ micro l). Maximum mobilization varied with median circulating CD34+ cells and colony forming units-granulocyte/macrophage (CFU-GM) peaks of 17.2/ micro l (range: 8.1-210) and 1,650/ml (range: 540-62,900), respectively. A median of two leukaphereses resulted in the harvesting of a median of 6.7x10(6) (range: 0.3-33.6) CD34+/kg and 21.1x10(4) (range: 1.2-209) CFU-GM/kg. Intensified therapy with intermediate-dose melphalan, associated or not with mitoxantrone, was delivered with autologous PBPC support to 13 patients and always resulted in rapid and stable hemopoietic reconstitution. The program was well tolerated and no treatment-related deaths occurred. Twelve patients are still alive with a 5-year survival projection of 59%. In conclusion, the results demonstrate the feasibility of using autologous PBPC to support therapy intensification even in elderly patients.

Increased hematopoietic stem cell mobilization in aged mice

“…Hematopoietic stem cell transplantation is most often administered to patients younger than 50 and rarely to patients older than 60 years of age 21,22 because the toxicity of the chemotherapy/ conditioning regimen has caused unacceptable morbidity in older patients. In contrast, the average age of patients at diagnosis of neoplasms (eg, leukemia, lymphoma) who are candidates for stem cell transplantation ranges from 65 to 70 years.…”

“…[18][19][20] The ability of healthy, older patients to undergo stem cell mobilization in response to granulocyte colony-stimulating factor (G-CSF), the standard regimen used for clinical HSPC mobilization, has thus far not been investigated in detail because autologous hematopoietic stem cell transplantation is most often administered to adults younger than 50 years and rarely to patients older than 60 years. 21,22 The limited available information is not conclusive in terms of efficiency of mobilization because it is based primarily on the analysis of mobilization of elderly patients after severe chemotherapy 23,24 and possibly also because 2 different methods of determining mobilization efficiency are used (colony-forming cell [CFC] frequency vs CD34 ϩ cell frequency in PB). Combining general clinical wisdom and these published reports, it is anticipated that the ability to mobilize HSPCs in response to G-CSF may be reduced in elderly patients, [23][24][25][26] hampering the efficient collection of HSPCs for subsequent hematopoietic stem cell therapies.…”

Autologous stem cell transplantation beyond 60 years of age

“…[56][57][58] Age per se does not seem to affect progenitor cell yield or success of mobilization in NHL patients mobilized with intermediate-dose CY plus G-CSF. 58,59 No randomized study has evaluated the feasibility and the efficacy of ASCT in elderly lymphoma patients but several single centre experiences 22,24,25,[59][60][61][62][63][64][65] and a nationwide analysis 66 have been published. These studies are shortly summarized in Table 2.…”

Autologous stem cell transplantation in elderly patients (>=60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry

“…[12][13][14][15][16][17][18] Only four series including at least 20 transplanted DLBCL patients over 60 years of age have been published. [19][20][21][22] Although these reports give some hints on early non-relapse mortality and outcome, they are too small to facilitate proper analysis of risk factors for non-relapse mortality or prognostic factors for long-term outcome.…”