An article abstract:

Significant predictors of treatment outcome are poorly defined for patients with T-lineage acute lymphoblastic leukemia (T-ALL). A high WBC at diagnosis, which has traditionally been a predictor of poor response in T-ALL, has considerably weakened prognostic significance in the face of modern, more intensive chemotherapy. To test the hypothesis that bone marrow stroma-supported leukemic cell recovery might identify children at high risk for relapse, we measured the ex vivo recovery of T-ALL lymphoblasts from 29 newly diagnosed patients using a stromal cell co-culture assay. In all cases the T-ALL lymphoblasts showed an increase in recovery of T-ALL cells (RTC), ranging from 4 to 343%, in comparison to samples maintained without stroma. Since we were blinded to patient outcome in this case-control study, we then correlated patient outcome with RTC. The RTC for 18 patients in complete continuous remission (CCR) for greater than 4 years was stochastically larger than for the 11 patients who eventually relapsed (P = 0.011, by the two-sided Wilcoxon test). Furthermore, 100% of patients with an RTC of more than 26% had a CCR greater than 4 years while 78% of the patients with an RTC of less than 25% relapsed within 4 years. This is the first report to show that higher lymphoblast recovery may predict a more favorable outcome for children with T-ALL. A prospective study is needed to test whether stroma-supported leukemic cell recovery might serve as a basis for assigning risk-adjusted therapy.

What is the meaning of recovery here? It puzzles me as a non-native speaker of English. Do the authors simply mean "the number of cells that survive"? Or is there some "recovery process" - if yes, what is the nature of this process?

P.S. The question arose from a question asked by a fellow translator. She translates a text in which T cells transduced with gene for a receptor against leukemic cells are co-cultured with such cells, after which

"T cells transduced with the receptor markedly reduced leukemic cell recovery".

The translator has trouble understanding how to put it in Russian, because translating "recovery" verbatim would imply some process in which a cell recovers, say, from injury.

Is "recovery" just "the percentage of cells that survived, relative to the overall number of cells"?

  • $\begingroup$ I don't think this is a great place to ask, unless a bona fide hematologist answers, and who can assure that? The term is confusing. In your place, I would check with a hematologist. It's not a common term. $\endgroup$ – anongoodnurse Apr 12 '18 at 21:45

TL;DR: Yes, it's just percentage of cells that survived. With the caveat that the assay doesn't give information on how much the number of cells is influenced by survival, dying, or growth rate.

"Recovery" in this context means "cells found after X amount of culture time". Generally speaking, recovery often refers to putting something in a program/dish/liquid/organism and seeing how much is still left after some processing/treatment/culture. For example, if I give a 1-year-old child 10 porcellain plates to play with, I might be interested in what percentage I can recover after 2h of play time. Of course in the context of cell culture, that percentage can be above 100% if the cells multiplied in the meantime.

As the methods of the article describe, the culture assay consists of first growing a single layer of stromal cells (HS-5 cells) on a culture plate for 24h. These cells provide support for the actual cells of interest. The researchers then spread 5.0 × 105 viable T-ALL lymphoblasts isolated from a patient sample on the stromal cell layer. They do this twice* for each sample, in one case collecting the cells after 1h (which isn't usually enough time for human cells to do anything), in the other case collecting them after 72h of culture (which is enough for healthy cells to grow substantially). Then they use flow cytometry to quantify how many T-ALL cells are now in the culture after that time has elapsed.

This helpful graphic is from the paper. The word "cells" in the formula refers to T-ALL cells.

The percentage of recovered T-ALL cells (RTC) was calculated by: The formula for calculating RTC is: viable cells after 72h divided by viable cells after 1h

Essentially, what the authors here studied is whether the likelihood of a T-ALL patient to relapse might be related to the ability of their cancerous cells to survive or grow in a culture dish coated with stromal cells.

The quote from your colleague would mean that the T cells were surviving/growing less or dying more if they were transduced with the receptor.

*rather, four times. Twice for 1h and twice for 72h collection. At least this is what "in duplicate" implies.

  • $\begingroup$ Why do the authors use ex vivo instead of in vitro for their culture? I found the term ambiguous, and only used 13 times (can't remember exactly) on Googling with Scholar. But nice answer. $\endgroup$ – anongoodnurse Apr 13 '18 at 19:41
  • $\begingroup$ In my understanding, ex vivo is a subclass of in vitro, although it's not something I would associate with primary culture of lymphoblasts... $\endgroup$ – Armatus Apr 16 '18 at 6:53
  • $\begingroup$ Thanks. My understanding of ex vivo is, say, bone marrow. But if it's cultured, it's not ex vivo (it's been grown.) Anyway, I didn't have full access, but thought the paper was not without ambiguities. Again, thanks. (btw, the term I found ambiguous was leukemic cell recovery). For a cancer so well studied, to find it so few times was interesting. $\endgroup$ – anongoodnurse Apr 16 '18 at 12:42

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