Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation

Pérez-Simón, Josè Antonio; Díez-Campelo, María; Martino, Rodrigo; Sureda, Anna; Caballero, Dolores; Cañizo, Consuelo del; Brunet, Salut; Altés, Albert; Vázquez, Lourdes; Sierra, Jordi; Miguel, Jesús F. San

doi:10.1182/blood-2002-11-3503

Cited by 101 publications

(102 citation statements)

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“…7,9,17 We and others have observed a strong association between GVHD and decreased risk of disease progression in both myeloid and lymphoid malignancies. 9,[18][19][20][21] The occurrence of moderate to severe GVHD, however, also increases the risk of developing life-threatening infections. [21][22][23][24] Elderly or debilitated patients tolerate GVHD and its treatment poorly, thus explaining our risk factors for TRM and OS.…”

Section: Discussionmentioning

confidence: 99%

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Gómez-Núñez

Martino

Caballero

et al. 2004

Bone Marrow Transplant

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Summary:Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients o60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age 460 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status 41. The 1-year TRM in patients with 0 or 1 and 42 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (Po0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors. Allogeneic stem cell transplantation (alloSCT) is a wellestablished treatment approach for numerous hematological malignancies. However, high-dose conditioning regimens designed to both control the malignancy and to prevent graft rejection are associated with a high mortality and a high incidence of acute and long-term side effects, especially in elderly or debilitated patients. A potential way to overcome this problem is by decreasing the intensity of chemotherapy and/or radiotherapy given prior to transplantation. Several groups of investigators have developed reduced-intensity conditioning (RIC) regimens that lead to successful engraftment in patients with hematological and nonhematological malignancies, without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6] Based on numerous phase II trials, RIC are able to induce graft-versus-leukemia/tumor (GVL) effects with acceptable levels of extrahematologic toxicity. Thus, these attenuated regimens have been used mostly in older patients or patients with pre-existing organ dysfunction who would otherwise have a high risk of transplant-related mortality (TRM) after a myeloablative alloSCT. To date however, risk factors for TRM and their impact on overall survival (OS) after RIC transplants have not been described. We report here results of a prospective multicenter study of two RIC regimens (for myeloid and lymphoid malignancies) followed by allogeneic peripheral blood SCT (PBSCT) that is being conducted in several institutions in Spain, with special emphasis on pretransplant variables that influenced early TRM and OS. Patients and methods Patient selectionEligibility criteria for entry into this RIC allogeneic PBSCT program included patients with a myeloid o...

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Section: Discussionmentioning

confidence: 99%

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Gómez-Núñez

Martino

Caballero

et al. 2004

Bone Marrow Transplant

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“…Perez-Simon et al 21 analyzed the impact of CD34 þ cell dose on the outcome for 86 patients with hematological malignancies after allo-PBSC from matched sibling donors, using a reducedintensity regimen. Conditioning consisted of fludarabine (total dose 150 mg/m 2 ) in combination with either melphalan (140 mg/m 2 ) or BU (10 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

Tsirigotis

Shapira

et al. 2009

Bone Marrow Transplant

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The influence of graft composition on the outcome of reduced-intensity (RIC) allogeneic PBSC transplantation (allo-PBSC) remains controversial. In this study, we analyzed the impact of CD34 þ cell dose on the incidence of GVHD, and on the outcome after allo-PBSC, in 103 patients with hematological malignancies, using a uniform RIC regimen. The following variables were included in statistical analysis: (1) number of C34 þ cells, (2) highrisk vs low-risk disease status, (3) matched related vs matched unrelated donor, (4) female donor to male recipient vs any other combination, (5) age of recipient (above vs below the median). Univariate and multivariate analysis did not reveal any association between CD34 þ cell dose and acute grade-2 to grade-4, cGVHD, nonrelapse mortality (NRM), relapse rate (RR) and OS. High-risk disease status was the only variable independently associated with increased NRM (P ¼ 0.001), increased RR (P ¼ 0.012) and decreased OS (Po0.001). The same results were obtained when analysis was restricted to a subgroup of 55 patients with myeloid neoplasms. The influence of graft composition on the outcome of RIC allo-PBSC should be further investigated via well-controlled randomized prospective studies.

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“…On the contrary, high CD34 þ cell doses have been associated with increase in risks of chronic GVHD and increases in mortality, with the possible exception of high risk patients receiving reduced intensity regimens. [5][6][7][8] In the setting of autologous peripheral blood stem cell transplantation, CD34 þ cell doses of 43 million/kg have been associated with better outcomes, primarily due to faster hematologic recovery and lower incidence of infectious and bleeding complications. [9][10][11] Bensinger et al demonstrated that infusing doses of o2 million CD34 per kg was associated with slower hematologic recovery and worse outcomes, whereas patients receiving 45 million CD34 per kg seemed to have a faster robust platelet recovery.…”

Section: Issues In Stem Cell Collectionmentioning

confidence: 99%

International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)

Giralt

Stadtmauer

Harousseau³

et al. 2009

Leukemia

209

165

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Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation

Abstract: We analyzed the impact of CD34 ؉ cell dose on the outcome of 86 patients undergoing reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation.

Cited by 101 publications

References 45 publications

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)

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