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Early and late graft-failure after transplants

Bone Marrow Transplantation volume 51, pages 182–183 (2016)Cite this article

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We have a high risk of being misunderstood by others or even confusing ourselves when using English words for medical conditions, especially when they suggest or imply the aetiology of a condition or event. Consider the terms primary and secondary. The Oxford English Dictionary (the Bible to most of us born pre-Wikipedia) defines primary as: of chief importance, principal, main, chief, key, principal, foremost predominant, overriding, major, ruling, dominant, master, supreme, cardinal, pre-eminent, ultimate. A parallel definition is: earliest in time or order, initial, original, beginning, first. Secondary, in contrast, is defined as: coming after, less important than, resulting from someone or something else that is primary, subordinate, lesser, minor, peripheral, tangential, marginal, ancillary, subsidiary, subservient, non-essential, unimportant or less important. But how are these terms used in medicine? Confusingly at best, incorrectly at worst.

Let us consider the use of these terms in the setting of a haematopoietic cell transplant. Persons failing to recover normal bone marrow function after a transplant are sometimes referred to as having primary graft-failure whereas persons with initial recovery of bone marrow function followed by deterioration or loss of bone marrow function are referred to as having secondary graft-failure. But what do these labels really mean? Is primary graft-failure the result of a non-functioning or poorly functioning graft (for example, the relevant haematopoietic cells may have been killed or incapacitated during the freezing or thawing processes), an abnormal bone marrow microenvironment, immune-mediated graft-rejection, exposure to drugs harmful to the graft, a combination of these or something(s) else? It is simplistic to suggest that only one mechanism might operate in a transplant recipient or that all transplant recipients with primary graft-failure have the same mechanism or combination of mechanisms. For example, in a study of persons with aplastic anaemia receiving a transplant from a genetically identical twin, about one-half of subjects recovered normal bone marrow function after the twin haematopoietic cells were infused.1 These persons were presumed to have aplastic anaemia from abnormal or absent haematopoietic stem or precursor cells, but a modern interpretation (which I regard as unlikely, but then again who am I to say?) is that their bone marrow microenvironment was defective and restored by unspecified cells in the graft other than haematopoietic stem or progenitor cells such as mesenchymal stromal cells. (I am reminded of the observation that pigs do not fly. But is it because they cannot fly or because they can but do not wish to?) However, the other one-half of recipients did not recover after the twin graft but another one-half of one-half recovered when a second bone marrow infusion was preceded by high-dose cyclophosphamide and were assumed to have immune-mediated aplastic anaemia. Interestingly, none of the recipients appeared to have an irreversible bone marrow microenvironment abnormality. These observations raise concerns regarding how we should interpret data from persons with so-called primary graft-failure.

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References

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  1. Division of Experimental Medicine, Department of Medicine, Haematology Research Centre, Imperial College London, London, UK

    R P Gale

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Correspondence to R P Gale.

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Gale, R. Early and late graft-failure after transplants. Bone Marrow Transplant 51, 182–183 (2016). https://doi.org/10.1038/bmt.2015.255

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