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Cold antibody autoimmune hemolytic anemia and lymphoproliferative disorders: a retrospective study of 20 patients including clinical, hematological, and molecular findings

Die autoimmunhämolytische Anämie vom Kältetyp: eine retrospektive Analyse von 20 Patienten unter Berücksichtigung klinischer, hämatologischer und molekularer Aspekte

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Summary

A total of 20 patients with cold antibody hemolytic anemia were evaluated in a retrospective study of them, 15 had a monoclonal gammopathy of unknown significance (MGUS): 14 with MGUS of immunoglobulin M (IgM) subtype and 1 with immunoglobulin G subtype. One patient had smoldering Waldenström’s macroglobulinemia, but four patients had no monoclonal protein and no evidence of lymphoma. However, in three of these patients, we were able to demonstrate a (mono-)clonal rearrangement of their immunoglobulin heavy and/or light chains. Of the 20 patients, 5 had IgHV34 nucleotide sequence indicating that the antibody was directed against the “I” antigen. Two patients exhibited a progressive increase of IgM over time, however without increasing hemolytic activity. Moreover, in two patients with long-term follow-up, we were able to correlate recurrent hemolytic activity with low environmental temperatures. Among four patients treated with rituximab, all four responded to treatment. However, treatment effect was only transient in all of them.

Zusammenfassung

Die primäre Kälteagglutininkrankheit (CAIHA, cold antibody immune hemolytic anemia) ist meist mit einem IgM Paraprotein als Ausdruck einer monoklonalen B-Zellerkrankung assoziiert. In der vorliegenden Studie wurden 20 Patienten mit primärer CAIHA retrospektiv analysiert. Bei 15 Patienten konnte eine monoklonale Gammopathie unklarer Signifkanz (MGUS) nachgewiesen werden, davon 14 mit einem IgM-Paraprotein und einer mit einem IgG-Paraprotein. Ein weiterer Patient hatte einen M. Waldenström, bei vier weiteren Patienten konnte jedoch kein Paraprotein nachgewiesen werden. Molekularbiologisch konnte jedoch auch bei drei von diesen vier ein monoklonales B-Zell Rezeptor Rearrangement nachgewiesen werden, wobei bei fünf von 20 Patienten das IgHV34 Segment rearrangiert war, welches mit Spezifität gegen das Blutgruppen „I“-Antigen assoziiert ist.

Bei zwei Patienten war im Beobachtungszeitraum ein Anstieg des IgM Paraproteins zu beobachten, dieser Anstieg war jedoch nicht mit einer Zunahme der Hämolyse assoziiert. Bei zwei Patienten mit ausserordentlich langer Beobachtungsdauer konnte jedoch ein Zusammenhang der hämolytischen Aktivität mit jahreszeitlichen Temperaturen beobachtet werden. Die Behandlung mit Rituximab führte bei vier von vier Patienten zu einer Besserung der CAIHA, der Erfolg der Behandlung bei allen Patienten war jedoch lediglich transient.

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Acknowledgment

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. This study has been reviewed at the local ethics committee (EK Nr. 061/2011), and informed consent was obtained from all patients for being included in the study.

Conflict of interest

Ulrich Jäger received honoraria and research support to MUW from Hoffmann-La Roche; the remaining authors declare no conflict of interest.

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Correspondence to Christian Sillaber MD.

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Arthold, C., Skrabs, C., Mitterbauer-Hohendanner, G. et al. Cold antibody autoimmune hemolytic anemia and lymphoproliferative disorders: a retrospective study of 20 patients including clinical, hematological, and molecular findings. Wien Klin Wochenschr 126, 376–382 (2014). https://doi.org/10.1007/s00508-014-0547-z

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