Page 19 - 2019_06-Haematologica-web

Editorials
Conditioning intensity and antilymphocyte globulin: towards personalized transplant strategies?
Martin Bornhäuser
Department of Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden and National Center for Tumor Disease (NCT), Germany
E-mail: MARTIN BORNHÄUSER - martin.bornhaeuser@uniklinikum-dresden.de doi:10.3324/haematol.2019.216952
In the last two decades allogeneic hematopoietic cell transplantation (HCT) has been used with increasing fre- quencies in hematologic malignancies with curative intent. The increased understanding of immune tolerance and allogeneic antileukemic immune reactivity has led sev- eral investigators to develop optimized conditioning proto- cols and new strategies to manipulate the effector cells either within the graft or in vivo.
More specifically, the development of minimal intensity or so called “nonmyeloablative” conditioning regimens paved the way towards the application of allogeneic HCT in older patients and all of those who probably would not tolerate classical intensity conditioning.1,2 The most fre- quently used protocol, spear-headed by investigators from the Fred Hutchinson Cancer Research Center, was based on a single dose of 200 cGy of total-body irradiation (TBI) and a few doses of fludarabine followed by pharmacological immunosuppression.3 After a wave of fascinating reports on the feasibility and efficacy of this “revolutionary” approach, some studies revealed that patients with a high risk of either disease recurrence or non-engraftment did not fare too well with this strategy.4 At the other end of the spec- trum, randomized comparisons suggested that less toxic
but still intensive conditioning with 800 cGy of fractionated TBI combined with fludarabine did not increase the rate of disease recurrence at the same time as significantly reducing extramedullary toxicity compared to 1200 cGy TBI with high-dose cyclophosphamide.5 Along these lines, Monaca and co-workers,6 again from Seattle, have convincingly demonstrated in this issue of Haematologica that subtle dose increases of unfractionated TBI can significantly decrease the failure rate after allogeneic HCT. Most interestingly, applying a differential dose escalation strategy, they identi- fied the optimal TBI dose for patients with high-risk myelodysplastic syndromes and chronic myelomonocytic leukemia (450 cGy) and patients with low-risk myelodys- plastic syndromes and myeloproliferative neoplasms (300 cGy). Intermediate doses of unfractionated TBI have been successfully used by other colleagues in diseases such as chronic myeloid leukemia.7 The current optimization of the nonmyeloablative protocol developed by the investigators in Seattle clearly shows that differential doses of TBI com- plement the most frequently applied protocols based on alkylating agents combined with purine analogs.
As stated above, the fine tuning of the allogeneic immune response by T-cell depletion or pharmacological means rep-
Figure 1. A personally tailored approach to hematopoietic cell transplantation. TBI; total body irradiation; CTX: chemotherapy; GvHD: graft-versus-host disease; HCT: hematopoietic cell transplantation.
haematologica | 2019; 104(6)
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