Blood and Marrow Transplantation Long Term Management. Группа авторов. Читать онлайн. Newlib. NEWLIB.NET

Автор: Группа авторов
Издательство: John Wiley & Sons Limited
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Жанр произведения: Медицина
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isbn: 9781119612735
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attenuates with extended follow‐up. A Japanese study of almost 18 000 survivors observed that 28% were lost to follow‐up by 10 years; 67% by 25 years [9]. Given that many HCT late effects have latency periods of 7–20 years, and children are generally expected to have longer life expectancy compared to their adult counterparts, this observation warrants a robust mitigation plan. Multivariate risk factors for LTFU termination include being aged 15–29 years, female, have standard risk malignancy or non‐malignant disease as the underlying reason for HCT, unrelated donor, and cGVHD. LTFU termination was mostly physician‐directed and based upon a patient being in good medical condition. Better physical condition might explain higher risk for LTFU termination among females; another study also suggested a greater concern for medical costs among females that might contribute to this observation [10]. Education of stakeholders must emphasize adherence to LTFU regardless of whether a young adult survivor appears well. Cooperation is needed between pediatric and adult systems to mitigate this known “lost in transition” phenomenon.

      There are few large‐scale studies or randomized trials to guide LTFU recommendations. Consortia have published organ‐system categorized guidelines based on expert opinion or limited high‐quality evidence. They are HCT‐focused and relatively concise but for a given complication they lack granularity regarding pre‐HCT treatment exposures and/or age [11]. By contrast, Children’s Oncology Group (COG), provides more granular LTFU guidelines specifically for survivors of childhood, adolescent, and young adult cancers but not exclusive to HCT survivors [12]. COG consensus guidelines, developed by a panel of experts, are updated every 5 years and version 5.0 was released in October 2018. Unlike joint society guidelines, COG organizes LTFU by therapeutic exposures and their impact on various organ systems, which is pertinent to this heavily pretreated population. Sixteen sections address HCT‐specific late effects, including 9 GVHD‐focused sections. COG also developed an HCT Task force to provide organ system categorized HCT [13].

Schematic illustration of the HCT late effects relate to exposures, genetics, age gender and lifestyle.

      Engraftment

      Engraftment definitions based on early neutrophil and platelet recovery are insufficient to address late graft failure and rejection because nonmyeloablative and reduced intensity conditioning often results in mixed donor chimerism in one or more leukocyte lineages. This is rarely an issue for children with heavily pretreated malignancies, though falling chimerism is followed closely by some centers with the goal of preemptive intervention for impending relapse. Beyond this rationale, chimerism monitoring during LTFU is of questionable value for malignant diseases unless confirmation of residual donor hematopoiesis is necessary before donor lymphocyte infusion.

      By contrast, mixed chimerism is essential in LTFU for NMDs, albeit dynamic patterns of lineage‐specific chimerism over months or years of follow‐up, and their meaning, remain to be firmly established for individual NMDs. What level of lineage‐specific chimerism is critical for durable correction of the underlying disease phenotype is also unclear for the full portfolio of NMDs [15,18]. Prospective LTFU studies are first needed to determine if complete donor chimerism is maintained in individual NMDs during extended LTFU. When mixed‐chimerism is present initially, or emerges over time, does the underlying disease phenotype, and/or autoimmunity, eventually return? For this reason, at least in primary immunodeficiency disease, the Primary Immunodeficiency Disease Transplant Consortium recommends lifelong, systematic and comprehensive assessment of lineage‐specific chimerism, plus numeric and functional immune reconstitution data, even if the patient is well and without signs of infection, to allow early detection and trajectory of possible declines in chimerism and immune function and so that intervention can occur before clinical complications of recurrent SCID emerge [17]. Testing begins no later than 3 months after HCT.

      Iron overload

      Iron overload occurs frequently after HCT [19,20], usually as a result of red blood cell (RBC) transfusions before and after HCT, ineffective erythropoiesis with intestinal hyperabsorption and, in some patients, underlying hereditary hemochromatosis (HH). Certain children are more at risk for iron overload and its consequences due to years of ineffective erythropoiesis before HCT (thalassemia, sickle cell disease) or, numerous RBC transfusions for marrow failure (Fanconi anemia [FA], Diamond‐Blackfan anemia [DBA], aplastic anemia) or relapsed hematologic malignancies. Once normal hematopoiesis is restored post‐HCT without need for RBC transfusions, body iron stores decline over several years [21]. However, accumulated iron may be high enough that intervention is recommended to prevent liver and cardiac failure.

Organ System or Late Effect Recommendations: Qualifiers and other comments:
Engraftment Annual CBC, MCV ± reticulocytes More frequently, if persistent or progressive abnormalities that may be due to medications, infection, GVHD, relapse
Flow cytometry‐sorted lineage specific donor chimerisms Minimum of annual in NMDs where long‐term graft stability is unclear (especially after NMT or RIC)SCD: check myeloid chimerism q3–6 months for 2 years, then yearly with HbS levelThalassemia: if microcytic anemia recurs check chimerism as for SCDUsually unnecessary in malignant diseases

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