The use of autologous haematopoietic stem cell transplantation (ASCT) has increased considerably in lymphoid malignancies in the last decade, and it is now considered as the standard of care in particular circumstances. This review aims to present an overview of the current situation with ASCT in lymphoid malignancies in Europe, in terms of both current use and issues. It will also look briefly at ASCT in rarer haematological malignancies and at the future. It is intended as a reflection of opinion from selected centres in Europe and as an aid to understanding for those who are new to the area. The review is based on a series of four preceptorship meetings held in Europe in 2013.

Current status of haematopoietic autologous stem cell transplantation in lymphoid malignancies: A European perspective

The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin’s lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored. Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP. The median CD34+ cell yield was 7.01 × 106 cells/kg body weight (range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ≥2.0 × 106 cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1–3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P = 0.01). No significant differences in toxicity or engraftment were observed between the two groups. The present study demonstrated that dose-adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.

/pdf/autologous-peripheral-blood-stem-cell-mobilization-following-ee64e4y2tk.pdf

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin’s lymphoma

Introduction: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome. Methods: The prospective, multicenter, open-label, non-interventional OPTIMOB study assessed mobilization and collection parameter of patients with lymphoma or multiple myeloma to get deep insights in the treatment of those patients in clinical routine focusing on PM patients. PM was defined as follows: (1) no achievement of ≥20 CD34+ progenitor cells/µL before first apheresis, (2) PLX administration at any time point during the observational period, (3) reduction of the initially planned CD34+ progenitor cell yield as necessity due to failed mobilization or HSC collection, and (4) no performance of apheresis due to low CD34+ progenitor level. Primary objective of the study was to assess mobilization success by the proportion of PM patients achieving >2 × 106 CD34+ progenitor cells/kg body weight on the first day of apheresis. Here, the data of the lymphoma cohort are presented. Results: Out of 238 patients with lymphoma documented in the study, 32% were classified as PM. 87% of them received PLX. Demographic data revealed no obvious differences between PM and good mobilizing (GM) patients. All patients were treated highly individualized prior to mobilization. Majority of all PM patients were able to undergo apheresis (95%) and reached their individual requested CD34+ progenitor cell target (72%). 57% of the PM patients achieved >2.0 × 106 CD34+ progenitor cells/kg body weight on day 1 of apheresis and nearby 70% of them underwent ASCT. Median time to engraftment was similar in PM and GM patients of the lymphoma cohort. Conclusions: Majority of PM patients with lymphoma were successfully mobilized and underwent ASCT. Most of them received PLX during the study.

Mobilization and Hematopoietic Stem Cell Collection in Poor Mobilizing Patients with Lymphoma: Final Results of the German OPTIMOB Study

L’autogreffe de cellules souches hematopoietiques (CSH) est un type de greffe dont les cellules a greffer proviennent du malade lui-meme. Lors de la mobilisation et du recueil de CSH, il existe une grande variabilite interindividuelle qualitative et quantitative des CSH, dont les causes ne sont toujours pas clairement etablies. A partir d’une cohorte de patients du CHU de Toulouse, nous avons etudie l’influence de differents facteurs sur la mobilisation de CSH ainsi que son recueil. Les donnees medicales ont ete recueillies retrospectivement pour les patients beneficiant d’un recueil de CSH entre 2014 et 2016. L’influence de differents facteurs a ete evaluee sur deux parametres principaux : la mobilisation et le recueil de CSH. Secondairement, la perte en CSH lors de la decongelation du greffon et le delai de sortie d’agranulocytose ont ete analyses. Apres analyses univariee et multivariee de facteurs selectionnes, un modele de regression lineaire a ete etabli pour chaque parametre. 319 patients etaient evaluables. La variabilite interindividuelle de mobilisation est peu expliquee par les caracteristiques patients, meme si l’IMC, le rituximab et le diagnostic de LNH indolent semblent l’influencer de facon positive et un traitement anterieur par lenalidomide, la radiotherapie, le diagnostic de LH et le sexe feminin de facon negative. Concernant le recueil de CSH, sa qualite est amelioree par le taux de CD34+ circulant et le recours au cyclophosphamide pour la mobilisation, alors qu’une induction contenant des IMIDs (lenalidomide et thalidomide) semble l’abaisser. Nos resultats permettent de cibler les facteurs a prendre en compte pour optimiser le recueil de CSH mais des etudes prospectives restent necessaires pour valider leur influence.

https://dumas.ccsd.cnrs.fr/dumas-01931478/document

Optimisation de l’utilisation du plerixafor : étude visant à identifier les facteurs de mauvaise mobilisation de cellules souches hématopoïétiques en vue d’une autogreffe

Rituximab (a chimeric anti-CD20 monoclonal antibody) is the first Food and Drug Administration approved anti-tumor antibody. Immunotherapy by rituximab, especially in combination-therapy, is a mainstay for a vast variety of B-cell malignancies therapy. Its therapeutic value is unquestionable, yet the mechanisms of action responsible for anti-tumor activity of rituximab and rituximab resistance mechanisms are not completely understood. Investigation of the mechanisms of action that contribute to the rituximab activity have eventually directed to a suite of novel combinations and novel treatment schedules, and also have resulted new generations of antibodies with more desired effects. Although, further investigations are needed to define the mechanisms of rituximab resistance and prominent effector activity of the altered next generation anti-CD20 to improve their efficacies and develop new anti-CD20 monoclonal antibodies in NHL treatment. This article focuses on the properties of CD20 which led scientists to select it as an effective therapeutic target and the molecular details of mechanisms of rituximab action and resistance. We also discuss about the impact of rituximab in monotherapy and in combination with chemotherapy regimens. Finally, we comparatively summarize the next generations of anti CD20 monoclonal antibodies to highlight their advantages relative to their ancestor: Rituximab.

A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections.

Impact of rituximab on stem cell mobilization following ACVBP regimen in poor-risk patients with diffuse large B-cell lymphoma: results from a large cohort of patients

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Impact of rituximab on stem cell mobilization following ACVBP regimen in poor-risk patients with diffuse large B-cell lymphoma: results from a large cohort of patients