Erratum: Modern approaches to HLA-haploidentical blood or marrow transplantation.

Abstract

Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately onethird of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival. Several novel approaches to HLA-haploidentical alloBMT have yielded encouraging results with high rates of successful engraftment, effective GVHD control and favourable outcomes. In fact, outcomes of several retrospective comparative studies seem similar to those seen using other allograft sources, including those of HLA-matched-sibling alloBMT. In this Review, we provide an overview of the three most-developed approaches to HLA-haploidentical alloBMT: T-cell depletion with 'megadose' CD34 + cells; granulocyte colonystimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We review the preclinical and biological data supporting each approach, results from major clinical studies, and completed or ongoing clinical studies comparing these approaches with other alloBMT platforms.

Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide

“…Even though PTCy is broadly and highly effective in preventing chronic GvHD in patients undergoing alloBMT, 1,2,4–6 our study has not revealed any factor that can prognosticate which of our patients will still develop chronic GvHD despite PTCy treatment. It is possible that the lack of any significant findings was due in part to the low incidence of chronic GvHD in our patients and thus low statistical power to detect true differences that may exist; however, the number of chronic GvHD events (n=24) was identical to the number of NRM events (n=24) and more than the number of grade III–IV acute GvHD events (n=18).…”

“…1 This approach has facilitated the safe performance of T-cell-replete human leukocyte antigen (HLA)-haploidentical alloBMT 1–3 and can function as single-agent GvHD prophylaxis after myeloablative conditioning and HLA-matched bone marrow allografting. 1,4–6 Despite these clinical successes with low rates of severe acute GvHD, chronic GvHD, and non-relapse mortality (NRM), biomarkers prognostic for GvHD or predictive for NRM occurring despite the use of PTCy have not been explored. Such biomarkers could potentially help guide treatment decisions and direct more intensive clinical surveillance of patients at high-risk for poor outcomes.…”

“…With the increasing use of PTCy worldwide and the clinical observations (e.g., low incidence of chronic GvHD) suggesting that PTCy may modulate GvHD risk in a dissimilar way to other T-cell-replete alloBMT approaches, 1 we explored whether these seven promising candidate biomarkers had utility in prognosticating clinical outcomes for PTCy-treated patients. We assessed plasma levels using blood previously collected at serial pre-determined timepoints from 158 patients treated on one of three prospective clinical studies of PTCy as GvHD prophylaxis after myeloablative alloBMT using either HLA-matched or HLA-haploidentical donors.…”

Physicians' preferences and perceptions regarding donor selection in allogeneic stem cell transplantation in Korea when a matched domestic donor is not available

“…This phenomenon is interesting because the outcomes with haplo-matched family donors are gradually improving, with some studies reporting outcomes similar to those with matched unrelated donors for haplo-HSCT [9]. The best haplo-HSCT results are being reported in AML patients, with results similar to those of allo-HSCT from matched sibling donors [1011].…”

Natural Killer Cells for Therapy of Leukemia

“…Allogeneic HSCT (allo-HSCT) has curative potential essentially through the immune-mediated graft-versus-leukemia (GvL) effect [16]. In contrast to total-body irradiation or chemotherapies, the immune effectors also eradicate malignant stem cells, thus minimizing the risk for disease relapse.…”