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Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update
Patel, P., Robinson, P. D., Baggott, C., Gibson, P., Ljungman, G., Massey, N., Ottaviani, G., Phillips, R., Revon-Rivière, G., Treister, N., et al
European journal of cancer (Oxford, England : 1990). 2021;154:92-101
Abstract
PURPOSE To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. METHODS We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis. RESULTS We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects. CONCLUSIONS Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.
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2.
[Palliative care in hematopoietic stem-cell transplanted patients: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Polomeni, A., Prod'homme, C., Ainaoui, M., Bellec, A., Berr, A., Bonneau, J., Charbonnier, A., Coiteux, V., de Berranger, E., Descamps, T., et al
Bulletin du cancer. 2021
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT), the only curative therapy for numerous hematological malignancies, carries a significant risk of morbidity and mortality. The patients and families' expectations regarding the procedure, the prognosis uncertainties, as well as the existence of potential new therapeutic possibilities, lead to frequent use of intensive care. Even though the transplant physicians are highly skilled in acute care, their knowledge of palliative approach is limited, making the use of palliative care insufficient and often late. By promoting reflection on the proportionality of care and the patients' quality of life, palliative care may contribute to the allo-HCT patients management. Nevertheless, obstacles to this approach remain. The objective of this work is to propose recommendations to promote the implementation of palliative care into transplant units.
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3.
Guidelines for the Prevention and Management of Graft-versus-Host Disease after Cord Blood Transplantation
Ponce, D. M., Politikos, I., Alousi, A., Carpenter, P. A., Milano, F., MacMillan, M. L., Barker, J. N., Horwitz, M. E.
Transplantation and cellular therapy. 2021;27(7):540-544
Abstract
The incidence of graft-versus-host disease (GVHD) after cord blood (CB) transplantation (CBT) is lower than expected given the marked degree of human leukocyte antigen (HLA)-mismatch of CB grafts. While the exact mechanism that underlies this biology remains unclear, it is hypothesized to be due to the low number of mostly immature T-cells infused as part of the graft1,2, and increased tolerance of CB-derived lymphocytes induced by the state of pregnancy. Nevertheless, acute GVHD (aGVHD) is a significant complication of CBT. In contrast, the incidence of chronic GVHD (cGVHD) following CBT is lower than what is observed following matched related or unrelated donor HSC transplantation (HSCT)3-6. This review outlines the guidelines for the prevention and management of acute and chronic GVHD following CBT.
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Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer
Ragoonanan, D., Khazal, S. J., Abdel-Azim, H., McCall, D., Cuglievan, B., Tambaro, F. P., Ahmad, A. H., Rowan, C. M., Gutierrez, C., Schadler, K., et al
Nature reviews. Clinical oncology. 2021
Abstract
Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.
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5.
Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents
Nabarrete, J. M., Pereira, A. Z., Garófolo, A., Seber, A., Venancio, A. M., Grecco, C. E. S., Bonfim, C. M. S., Nakamura, C. H., Fernandes, D., Campos, D. J., et al
Einstein (Sao Paulo, Brazil). 2021;19:eAE5254
Abstract
The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian Society of Bone Marrow Transplantation. Publisher: Abstract available from the publisher. por
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Worldwide Network for Blood and Marrow Transplantation (WBMT) Recommendations Regarding Essential Medications Required To Establish An Early Stage Hematopoietic Cell Transplantation Program
El Fakih, R., Greinix, H., Koh, M., Shaw, B., Mohty, M., Al Nahedh, M., Saber, W., Kharfan-Dabaja, M. A., Perales, M. A., Savani, B. N., et al
Transplantation and cellular therapy. 2021;27(3):267.e1-267.e5
Abstract
Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.
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National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report
Williams, K. M., Inamoto, Y., Im, A., Hamilton, B., Koreth, J., Arora, M., Pusic, I., Mays, J. W., Carpenter, P. A., Luznik, L., et al
Transplantation and cellular therapy. 2021
Abstract
Preventing chronic graft-versus-host disease (GVHD) remains challenging because the unique cellular and molecular pathways that incite chronic GVHD are poorly understood. One major point of intervention for potential prevention of chronic GVHD occurs at the time of transplantation when acute donor anti-recipient immune responses first set the events in motion that result in chronic GVHD. After transplantation, additional insults causing tissue injury can incite aberrant immune responses and loss of tolerance, further contributing to chronic GVHD. Points of intervention are actively being identified so that chronic GVHD initiation pathways can be targeted without affecting immune function. The major objective in the field is to continue basic studies and to translate what is learned about etiopathology to develop targeted prevention strategies that decrease the risk of morbid chronic GVHD without increasing the risks of cancer relapse or infection. Development of strategies to predict the risk of developing debilitating or deadly chronic GVHD is a high research priority. This working group recommends further interrogation into the mechanisms underpinning chronic GVHD development, and we highlight considerations for future trial design in prevention trials.
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8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation
Groll, A. H., Pana, D., Lanternier, F., Mesini, A., Ammann, R. A., Averbuch, D., Castagnola, E., Cesaro, S., Engelhard, D., Garcia-Vidal, C., et al
The Lancet. Oncology. 2021;22(6):e254-e269
Abstract
Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.
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Candidacy for Extracorporeal Life Support in Children After Hematopoietic Cell Transplantation: A Position Paper From the Pediatric Acute Lung Injury and Sepsis Investigators Network's Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup
Zinter, M. S., McArthur, J., Duncan, C., Adams, R., Kreml, E., Dalton, H., Abdel-Azim, H., Rowan, C. M., Gertz, S. J., Mahadeo, K. M., et al
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2021
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Free full text
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Abstract
OBJECTIVES The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients. DATA SOURCES All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation. STUDY SELECTION All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems). DATA EXTRACTION All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions. DATA SYNTHESIS Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process. CONCLUSIONS Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.
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[Definition and standardization of histocompatibility requests depending on patient course and donor type: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) and the Francophone Society of Histocompatibility and Immunogenetics (SFHI)]
Dubois, V., Amokrane, K., Crocchiolo, R., Fort, M., Guillaume, N., Kennel, A., Michiels, S., Ralazamahaleo, M., Rouzaire, P. O., Yakoub-Agha, I., et al
Bulletin du cancer. 2021
Abstract
Standardization of histocompatibility tests for allogeneic hematopoietic cell transplants, harmonization of information transmitted to clinicians are part of quality improvement and optimization of human and economic resources. New HLA typing technologies provide high-resolution information within a reasonable time frame. Knowledge of high-resolution HLA typing for the patient and their relatives is essential for a better interpretation of compatibilities. HLA-DPB1 typing must be considered in transplant field regardless of the donor type. The benefits of using search and match programs are considerable. It saves time and reduces additional typing costs by providing rapid information about the likelihood to identify a matched unrelated donor. A backup therapy considering alternative cell sources or treatment can therefore be quickly implemented. The importance of knowledge and consideration of patient immunization for donor choice was explored in previous workshops of the SFGM-TC (2018 and 2019). The published recommendations remain applicable. The routine follow-up protocol and in case of desensitization will be detailed here. This harmonization must be accompanied by the standardization of information to be returned to the clinician regarding the donor finding possibilities for the patient. This will guarantee a similar quality level in every center.