Elsevier

Cytotherapy

Volume 8, Issue 1, 2006, Pages 79-88
Cytotherapy

Quality assessment of autografting by probability evaluation: model estimation by clinical end-points in newly diagnosed multiple myeloma patients

https://doi.org/10.1080/14653240500499549Get rights and content

Background

Pre-transplant clinical evaluation of autografting is an important step in predicting post-transplant support, complications and safety. Today, unfavorable outcomes such as early death or graft failure are rare, making them unsuitable for quality assessment of supportive autografting. However, end-points constructed from frequently occurring clinical events may estimate clinically relevant prognostic models.

Methods

The present retrospective analysis was based on two consecutive clinical trials in the Nordic area, including up to 640 newly diagnosed multiple myeloma patients.

Results

In the model, the efficacy (time on antibiotics and use of transfusions) was influenced by pre-transplant variables, including sex, nationality, serum creatinine, hemoglobin, disease stage at diagnosis, response following induction therapy, length of priming and average graft CD34+ cell number per day of harvest. The toxicity end-point (time to blood cell recovery) was influenced by nationality, marrow plasma cell percentage, serum creatinine, M-component isotype, response to induction therapy, length of priming and graft CD34+ cell number. The safety (early disease recurrence or death) was influenced by serum creatinine, hemoglobin, treatment response and CD34+ cell number.

Discussion

In conclusion, the model illustrates that intervention strategies in quality assessment of autografting may benefit from probability estimates of graded clinical end-points.

Introduction

High-dose therapy with autologous stem cell support is effective in younger patients with newly diagnosed multiple myeloma [1, 2]. Recently, survival data from prospective, population-based Nordic studies (NMSG no. 5/94 and no. 7/98) have been published, documenting a significant survival advantage compared with conventionally treated historical controls [3, 4]. Before study initiation in 1994, it was decided to establish a collaboration with a focus on evidence-based quality assessment of the hematopoietic progenitor and stem cell grafts (HPSC). Following three workshops on enumeration of CD34+ cells by flow cytometry [5., 6., 7.], a Nordic standard was recommended throughout the NMSG 5/94 and 7/98 studies with a recommendation to harvest >2 million CD34+ cells/kg bodyweight for autografting. The aim of the supportive autografting was to reduce the side-effects from high-dose therapy and avoid procedure-related health disadvantages for the patients at the lowest possible cost and resource expenditure [8].

Economic evaluation of health care is becoming increasingly important. Clinical end-points for such evaluations have recently been proposed [9]. The first objective of this proposal was to analyze efficacy, which in the context of post-transplant supportive care may be defined by, for example, days on antibiotics and transfusions of blood products. The second objective was to analyze toxicity defined by time to blood cell recovery. The third objective was to analyze safety as defined by risk of early relapse or death. Based on such retrospective analyses, we have estimated prognostic models regarding the short-term graded end-points in a homogeneous group of patients with multiple myeloma treated in a common Nordic protocol (NMSG 5/94 and 7/98).

The present study has identified prognostic variables and models, which may be useful in future individual pre-transplant probability evaluations.

Section snippets

Patient characteristics

Between 1994 and 2001, 14 centers in Denmark, Norway and Sweden enrolled 640 patients younger than 60 years (NMSG 5/94) and 65 years (NMSG 7/98) [3] with newly diagnosed, symptomatic multiple myeloma in a prospective, population-based study evaluating high-dose therapy with stem cell support. The present study included 529 patients treated in accordance with the protocol and excluded 111 non-transplanted patients as a result of early death, progressive disease following induction therapy,

Prognostic variables and models for efficacy of autografting

The distribution of patients obtaining a favorable, intermediate or unfavorable graded clinical outcome is given in Table 2. The efficacy end-point, describing cost/expenditure of supportive care, was influenced by eight out of the 13 analyzed potential predictors (Table 1). These were sex, nationality, disease stage, s-creatinine, hemoglobin, response to induction treatment, length of priming and average graft CD34+ cells harvested per day of leukapheresis (Table 3).

Further analysis revealed

Discussion

In the Nordic area, introduction of harvest procedures and quality assessment of blood autografts have been mandatory for the successful outcome of high-dose therapy in multiple myeloma [3]. The present report describes a retrospective analysis of the graft quality assessment program [5., 6., 7.], making use of recently proposed clinically based graded end-points (Table 1) [9]. First, grading of cost/expenditure for post-transplant supportive care (efficacy) was defined by length of antibiotic

Acknowledgements

This study is supported by research grants from the Nordic Cancer Union (grant no 56–9350/56–9351 and 56 100 02–9101/9102 95) and Danish Cancer Society (grant no 945 100–15).

Clinical data were based on the NMSG database (study NMSG numbers 5/94 and 7/98) from the Oncology Center in Lund, Sweden.

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    • Individual Quality Assessment of Autografting by Probability Estimation for Clinical Endpoints: A Prospective Validation Study from the European Group for Blood and Marrow Transplantation

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