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Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR‐ligand mismatch after dose‐reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma
Author(s) -
Kröger Nicolaus,
Shaw Bronwen,
Iacobelli Simona,
Zabelina Tatjana,
Peggs Karl,
Shimoni Avichai,
Nagler Ar,
Binder Thomas,
Eiermann Thomas,
Madrigal Alejandro,
Schwerdtfeger Rainer,
Kiehl Michael,
Sayer Herbert Gottfried,
Beyer Jörg,
Bornhäuser Martin,
Ayuk Francis,
Zander Axel Rolf,
Marks David I.
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05513.x
Subject(s) - alemtuzumab , medicine , multiple myeloma , hazard ratio , gastroenterology , melphalan , cumulative incidence , transplantation , immunology , hematopoietic stem cell transplantation , graft versus host disease , confidence interval
Summary We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen‐matched or ‐mismatched unrelated donors. The ATG group had more prior high‐dose chemotherapies ( P < 0·001), while bone marrow was used more as the stem cell source in the alemtuzumab group ( P < 0·001). Alemtuzumab resulted in faster engraftment of leucocytes ( P = 0·03) and platelets ( P = 0·02) and in a lower incidence of acute graft versus host disease (GvHD) grades II–IV (24% vs. 47%, P = 0·06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0·001). The cumulative incidence of treatment‐related mortality at 2 years was 26% [95% confidence interval (CI) = 12–37%] for ATG vs. 28% (95% CI = 15–55%) for alemtuzumab, P = 0·7. There was no significant difference in the estimated 2‐year overall and progression‐free survival between ATG and alemtuzumab: 54% (95% CI: 39–75%) vs. 45% (95% CI: 28–73%) and 30% (95% CI: 16–55%) vs. 36% (95% CI: 20–62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2·37; P = 0·05) while killer immunoglobulin‐like receptor (KIR)‐ligand mismatch was protective for relapse ( P < 0·0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR‐ligand mismatched transplantation in multiple myeloma.