Standardization in hematology and wine

One thing every medical student should be taught, at a very early stage in their education, is that no two patients are the same. However, in our ‘tick-box’ culture, common sense seems to have disappeared and the ability to think for one’s self has been lost [1]. To give you an example: The Health Service Executive in Ireland launched a campaign for vaccination against SARS CoV-2 for patients over 70 years of age. Our family doctor’s secretary telephoned my wife to make an appointment for her and asked her ‘was she pregnant? Obviously, it was on the list of questions and had to be asked however totally irrelevant [2]. It seems to me that there is a massive drive, at least in the USA and Europe, to standardize everything from coffee to HCT. For some of us, in certain circumstances, standardization is a good thing. It is reassuring, for example, for passengers to know that all airline pilots use the same standards for take-off and landing (standard operating practise. (S.O.P.) But these rigid standards may not be of benefit to all in all circumstances and may lead to a certain sameness when as we know variety is ‘the spice of life’. Standardization and normalization are created to achieve a similar result. Technically standardization is the subtraction of the mean, and then division by its standard deviation while normalization is the process of dividing a vector by its length and the transformation of data into a range between 0 and 1. For those of us who are not well versed in statistical theory, it suffices to say that most hematologists would like to know that there is a minimum number of mononuclear cells from the donor required for successful allogeneic HCT. However even this number is not known and will probably never be known in HCT, as currently performed. In practice, most hematologists will be satisfied if the number of donor nucleated cells collected reaches >1.0 × 10/kg recipient body weight. Numbers below this may suffice for successful engraftment but graft failure in the setting of allogeneic HCT is extremely rare, excluding HCT for severe aplastic anemia. The European Society for Blood and Marrow Transplantation (EBMT) and FACT (Functional assessment of cancer therapy) have been established to standardize HCT to improve all aspects of cellular therapy. The EBMT publishes a handbook in which there are detailed chapters on all aspects of HCT [3]. Randomized prospective clinical trials are notoriously difficult to conduct in most clinical areas of HCT and most recommendations are set by international teams of world-renowned experts. Although the recommendations are evidence-based we all know that evidence is subjective and not objective and most of these recommendations have not been subjected to rigorous statistical analysis and may never be. At a job interview, some years ago, I was asked by a nonmedical interviewer: how would I know if my HCT program had been a success? I answered: if most recipients came to the Christmas party 2–3 years after their HCT. This answer may seem a little simplistic, but as disease relapse following allogeneic HCT for acute myeloid leukemia remains the most common cause of HCT failure, perhaps it was not that wide of the mark. One of the most useful publications by the EBMT, in my view, is a summary of the cumulative results of HCT in Europe. Assuming that the results are always honest, it is a useful check on the results of your own HCT activity. One of the amazing things, to me, is the wide disparity in different countries in HCT activity [4]. It may be that the technique of collecting donor cells is standardized but the indications for HCT vary widely from country to country. The use of mobilized peripheral blood as the donor inoculum has outstripped the use of bone marrow cells, despite clear evidence that bone marrow is the preferred material when carrying out HCT for severe aplastic anemia. Is standardization in wine making a good thing? Yes and no! One of the joys of wine drinking is the alteration in taste between different vintages and the difference in taste between wines that are made from similar grapes in vineyards which are in proximity. One of the most widely known efforts at standardization, is the Gallo Nero (black rooster) symbol on many wines in Tuscany Fig. 2, [5, 6]. The area of Chianti Classico stretches from San Casciano, just south of Florence, to Castelnuovo Berardenga, near Siena. The predominant grape in Chianti is Sangiovese and in Chianti Classico the wine must be made from 80% Sangiovese and no white grapes are permitted. The main towns in the Chianti

'Well, gentlemen, so far as drinking is concerned, you have my hearty approval; for wine does of a truth moisten the soul and lull our griefs to sleep…at the same time awaking kindly feelings as oil quickens a flame…' Socrates, 470-399 BC. Greek Philosopher. Fig. 1.
One thing every medical student should be taught, at a very early stage in their education, is that no two patients are the same. However, in our 'tick-box' culture, common sense seems to have disappeared and the ability to think for one's self has been lost [1]. To give you an example: The Health Service Executive in Ireland launched a campaign for vaccination against SARS CoV-2 for patients over 70 years of age. Our family doctor's secretary telephoned my wife to make an appointment for her and asked her 'was she pregnant? Obviously, it was on the list of questions and had to be asked however totally irrelevant [2].
It seems to me that there is a massive drive, at least in the USA and Europe, to standardize everything from coffee to HCT. For some of us, in certain circumstances, standardization is a good thing. It is reassuring, for example, for passengers to know that all airline pilots use the same standards for take-off and landing (standard operating practise. (S.O.P.) But these rigid standards may not be of benefit to all in all circumstances and may lead to a certain sameness when as we know variety is 'the spice of life'. Standardization and normalization are created to achieve a similar result. Technically standardization is the subtraction of the mean, and then division by its standard deviation while normalization is the process of dividing a vector by its length and the transformation of data into a range between 0 and 1. For those of us who are not well versed in statistical theory, it suffices to say that most hematologists would like to know that there is a minimum number of mononuclear cells from the donor required for successful allogeneic HCT. However even this number is not known and will probably never be known in HCT, as currently performed. In practice, most hematologists will be satisfied if the number of donor nucleated cells collected reaches >1.0 × 10 8 /kg recipient body weight. Numbers below this may suffice for successful engraftment but graft failure in the setting of allogeneic HCT is extremely rare, excluding HCT for severe aplastic anemia.
The European Society for Blood and Marrow Transplantation (EBMT) and FACT (Functional assessment of cancer therapy) have been established to standardize HCT to improve all aspects of cellular therapy. The EBMT publishes a handbook in which there are detailed chapters on all aspects of HCT [3]. Randomized prospective clinical trials are notoriously difficult to conduct in most clinical areas of HCT and most recommendations are set by international teams of world-renowned experts. Although the recommendations are evidence-based we all know that evidence is subjective and not objective and most of these recommendations have not been subjected to rigorous statistical analysis and may never be.
At a job interview, some years ago, I was asked by a nonmedical interviewer: how would I know if my HCT program had been a success? I answered: if most recipients came to the Christmas party 2-3 years after their HCT. This answer may seem a little simplistic, but as disease relapse following allogeneic HCT for acute myeloid leukemia remains the most common cause of HCT failure, perhaps it was not that wide of the mark. One of the most useful publications by the EBMT, in my view, is a summary of the cumulative results of HCT in Europe. Assuming that the results are always honest, it is a useful check on the results of your own HCT activity. One of the amazing things, to me, is the wide disparity in different countries in HCT activity [4]. It may be that the technique of collecting donor cells is standardized but the indications for HCT vary widely from country to country. The use of mobilized peripheral blood as the donor inoculum has outstripped the use of bone marrow cells, despite clear evidence that bone marrow is the preferred material when carrying out HCT for severe aplastic anemia.
Is standardization in wine making a good thing? Yes and no! One of the joys of wine drinking is the alteration in taste between different vintages and the difference in taste between wines that are made from similar grapes in vineyards which are in proximity. One of the most widely known efforts at standardization, is the Gallo Nero (black rooster) symbol on many wines in Tuscany Fig. 2, [5,6]. The area of Chianti Classico stretches from San Casciano, just south of Florence, to Castelnuovo Berardenga, near Siena.
The predominant grape in Chianti is Sangiovese and in Chianti Classico the wine must be made from 80% Sangiovese and no white grapes are permitted. The main towns in the Chianti Classico area are Greve, Fig. 3 [3], Radda, Gaiole and Castellina but wines differ in taste because of variations in soil, elevation of vineyards, the clone of Sangiovese used, fermentation techniques and methods of storage. The symbol of the black rooster against a red background can be seen on bottles of Chianti Classico. In 1716 the Grans Duke of Tuscany, Cosimo III, fixed the borders of the Chianti region. In 1932 a ministerial decree defined the Chianti Classico area and 5 other areas. In 1996 Chianti Classico became an independent DOCG (controlled and Guaranteed Denomination of Origin). Special requirements for Chianti Classico are that production of wine may not begin until 4 years after planting and wines must have a minimum alcoholic level of 12 degrees and 12.5 degrees for Riserva.
There probably many other areas in the world where attempts at standardization of wines are practised. This standardization is most notable to the wine drinker but may be disadvantageous in that wines from some large producers tend to have the same taste from year to year. There is an attempt to develop the so-called 'international taste' This may be a good marketing ploy but nullifies the unexpected pleasure of the difference of wines from different vintages, and locations in the same region which may be more notable from small producers.
Finally, wine drinking is a matter of taste and context and many consumers may prefer consistency from year to year. Whatever your taste, standardization in hematology or wine making should never dull your quest for improvement in either area.