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

Abstract

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and <3 transfusions, ≤21 to 25 days in hospital or ≥7 days on antibiotics and no transfusions; from 21 to 30 days [25 to 34] in hospital), unfavorable (>7 days on antibiotics, >3 but <6 transfusions; >30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 10(6)/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 10(6)/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P < .0001) except acute myelogenous leukemia and acute lymphoblastic leukemia, (3) 1 or 2 aphereses (P = .001) predicted good outcome, (4) toxicity increased with higher graft volume reinfused (>500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care.

A comparative analysis of biosimilar vs. originator filgrastim in combination with plerixafor for stem cell mobilization in lymphoma and multiple myeloma: a propensity‐score weighted multicenter approach

“…Different single-institution retrospective studies compared mobilization kinetics of patients given biosimilar G-CSFs or originator compound, overall reporting equivalent activity. [1][2][3] However, extremely little evidence is available about comparative efficacy of biosimilar and originator compounds when G-CSF is combined with plerixafor to rescue patients at high risk of mobilization failure. 4 We herein report the results of a retrospective analysis of 296 patients affected by multiple myeloma (MM), non-Hodgkin (NHL), or Hodgkin lymphoma (HL) who underwent PBSC mobilization with G-CSF and plerixafor as part of the mobilizing strategy at 22 italian centers from January 2008 to December 2016 (patient characteristics are presented in Supporting Information Table 1).…”

Atypical CD4+/CD8+ Lymphocytosis and Prolonged Pancytopenia Associated With Human Herpesvirus 6 Reactivation After Autologous Peripheral Blood Stem Cell Transplantation

“…Previous literature reports at most a modest delay in hematological recovery following active HHV-6 infection for both allogeneic and autologous HCT, with a median duration of neutropenia of 12.5 days (range, 6-21 days) 2 . However, this does not drastically differ from neutrophil aplasia experienced by patients undergoing their first autologous PBSCT, where the median time to neutrophil engraftment was 12 days (range, 9-25 days) 13 . Extremely prolonged pancytopenia and graft failure associated with HHV-6 reactivation are well-recognized after allogeneic HCT 14,15 , but to our knowledge have not been extensively reported after autologous HCT.…”

“…In our case, neutrophil recovery did not occur until 38 days after first PBSCT. Extreme delay in neutrophil recovery after autologous PBSCT is decidedly uncommon; in 397 patients undergoing first autologous PBSCT, median time to neutrophil engraftment was 12 days (range, 9 to 25 days) 13 . Although the patient received a second infusion of autologous PBSCs at day +34 because of concern for primary graft failure, the recovery of neutrophils just four days later strongly indicates that the initial transplant was responsible for hematopoietic recovery.…”

Myeloablative I-131-Tositumomab with Escalating Doses of Fludarabine and Autologous Hematopoietic Transplantation for Adults Age ≥ 60 Years with B Cell Lymphoma

“…A recent validation study from the EBMT suggests that the maximum acceptable time in the hospital for lymphoma patients undergoing autologous transplantation is 25 days, much longer than our patients experienced. (25) Our current studies focus on the therapeutic use of isotopes such as 90 Y which are free of appreciable gamma emissions targeting either CD20 or CD45, further reducing the potential economic cost and broadening the applicability of this approach. (26, 27)…”