Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.

Summary:The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients р70 kg received 300 g/day and Ͼ70 kg 480 g/day. All patients were reinfused with PBPCs with a CD34 + cell count Ͼ2.0 × 10 6 /kg. Baseline characteristics of age, sex and CD34 + cell count were similar between the two arms, the median CD34 + cell count being 5.87 × 10 6 /kg in the day +1 group and 7.70 × 10 6 /kg in the day +7 group (P = 0.7). The median time to reach a neutrophil count of Ͼ0.5 × 10 9 /l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P = 0.68). Similarly, there was no difference in median days to platelet recovery Ͼ20 000 × 10 9 /l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P = 0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P = 0.7), intravenous antibiotic use (7 vs 8 days; P = 0.54) or median number of red blood cell transfusions (4 vs 7 units; P = 0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P Ͻ 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation

Bence‐Bruckler

Bredeson

Atkins

et al. 1998

“…These findings are consistent with previously published data in lymphoid malignancies and solid tumors. [26][27][28] In the meta-analysis of randomized controlled trials, the prophylactic use of growth factors after auto-SCT was associated with faster neutrophil recovery, reduction of days of parenteral antibiotics and hospital stay. 29 These benefits, however, did not translate into a reduction of NRM.…”

Section: Discussionmentioning

confidence: 99%

Use of G-CSF to hasten neutrophil recovery after auto-SCT for AML is not associated with increased relapse incidence: a report from the Acute Leukemia Working Party of the EBMT

Czerw

Labopin

Gorin

et al. 2014

Application of G-CSF in AML is controversial as leukemic blasts may express receptors interacting with the cytokine, which may stimulate leukemia growth. We retrospectively analyzed the impact of G-CSF use to accelerate neutrophil recovery after auto-SCT on outcome. Adults with AML in first CR autografted between 1994 and 2010 were included. Nine hundred and seventy two patients were treated with G-CSF after auto-SCT whereas 1121 were not. BM and PB were used as a source of stem cells in 454 (22%) and 1639 (78%) cases, respectively. The incidence of relapse at 5 years in the BM-auto-SCT group was 38% for patients receiving post-transplant G-CSF and 43% for those not treated with G-CSF, P = 0.46. In the PB-auto-SCT cohort, respective probabilities were 48% and 49%, P = 0.49. No impact of the use of G-CSF could be demonstrated with respect to the probability of leukemia-free survival: in the BM-auto-SCT group, 51% for G-CSF(+) and 48% for G-CSF(− ), P = 0.73; in PB-auto-SCT group, 42% for G-CSF(+) and 43% for G-CSF( − ), P = 0.83. Although G-CSF administration significantly shortened the neutropenic phase, no beneficial effect was observed with regard to non-relapse mortality. In patients with AML, the use of G-CSF after auto-SCT is not associated with increased risk of relapse irrespective of the source of stem cells used.Bone Marrow Transplantation (2014) 49, 950-954;

“…20,21 Obviously, the influence of all these parameters results in important differences in the seeding efficiency reported by different laboratories, thus accounting for remarkable uncertainties in estimating, for example, the number of colony-forming units (CFUs) to be considered in hematopoietic transplantation. 7,9,[22][23][24][25] The development of new biotechnology companies producing defined culture media now offers the possibility of using standardized culture conditions, something which will most probably improve the reproducibility of results related to the culture of hematopoietic progenitors, 26 albeit at the expense of increasing the costs of cell culture laboratories.With the aim of initiating a national program of standardization of clonogenic cultures, we have conducted a multicenter intercomparative study of in vitro cell cultures, which involved a total of 28 laboratories from 27 different institutions working on basic and clinical hematopoietic research. In particular, we have focused our interests on the standardization of human CFU-GM, BFU-E and CFU-GEMM assays.…”

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confidence: 99%

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confidence: 99%

Conclusions of a national multicenter intercomparative study of in vitro cultures of human hematopoietic progenitors

Lamana

Albella

Rodríguez

et al. 1999

Summary:With the aim of developing a standardized program of clonogenic cultures, a multicenter intercomparative study of human CFU-GM, BFU-E and CFU-GEMM cultures was conducted. Aliquots of fresh mononuclear cord blood cells, as well as uniform culture materials and instructions for cell culture and for colony scoring were distributed to 28 national laboratories involved in hematopoietic research and transplantation. High interlaboratory coefficients of variation (CV) in the reported number of progenitors were found in our first intercomparative study (range 67-231%). To investigate the relevance of colony scoring in variations of the reported colony numbers, participants were invited to attend a meeting where a single culture dish was scored. In this case, the CVs ranged from 31% to 81%. A subsequent intercomparative assay was then conducted, and significant reductions in the inter-laboratory CVs were obtained with respect to the first study (CVs for colonies grown with two different media: CFU-GMs, 48% and 55%; BFU-Es, 70% and 62%; CFU-GEMMs, 70% and 51%; respectively). In most instances CVs were not significantly different from those obtained in the single plate scoring study, suggesting that the scoring process was the most relevant parameter accounting for variations in the reported colony numbers. Keywords: clonogenic cultures; multicentric intercomparison; hematopoietic progenitors; standardization The finding, about 30 years ago, that the hematopoietic progenitors could be assayed by clonogenic cultures 1,2 has resulted in one of the most helpful tools in modern hematology. In the field of hematopoietic transplantation, in vitro cultures are widely used for evaluating the functional abilities of grafts for transplantation into recipients. [3][4][5][6][7][8][9][10][11][12] Although flow cytometry now offers the possibility of rapidly estimating the quality of the grafts by quantifying CD34 + cells, [13][14] this technology provides complementary rather than alternative information to that offered by in vitro assays. 15 This is most evident when considering the proliferative integrity of clonogenic progenitors, a population which only represents a subset -less than 30-40% -of the CD34 + pool. [16][17][18] Besides the field of hematopoietic transplantation, in vitro culture technology also constitutes a routine tool for researchers working in molecular hematology and gene therapy, since it provides essential information regarding the functions of new cloned genes in hematopoietic regulation.Because of the vast number of groups using clonogenic assays nowadays, a wide variety of culture procedures and stimulatory sources are frequently described in the literature. 19 In addition to this, the criteria for scoring colonies, and even the subjective interpretation of these criteria frequently vary between groups. 20,21 Obviously, the influence of all these parameters results in important differences in the seeding efficiency reported by different laboratories, thus accounting for remarkable uncertainties in est...