Successful Autologous Hematopoietic Progenitor Cell Transplantation in a Patient with an Isoantibody Against CD36(Glycoprotein IV, Nak A)
Total Page：16
File Type：pdf, Size：1020Kb
Bone Marrow Transplantation (2008) 42, 489–491 & 2008 Macmillan Publishers Limited All rights reserved 0268-3369/08 $32.00 www.nature.com/bmt LETTER TO THE EDITOR Successful autologous hematopoietic progenitor cell transplantation in a patient with an isoantibody against CD36(glycoprotein IV, Nak a) Bone Marrow Transplantation (2008) 42, 489–491; an anti-CD36 control alloantiserum (FER, kindly provided doi:10.1038/bmt.2008.190; published online 14 July 2008 by Ph. Bierling, Paris, France). GPIV deficiency was demonstrated by flow cytometry on both the patient’s platelets and monocytes using the CD36 monoclonal Refractoriness to platelet transfusions in patients under- antibody clone FA6.152 (Immunotech, Marseille, France), going myeloablative conditioning with consecutive hema- suggesting type I deficiency (Figure 1). In addition, his topoietic progenitor cell transplantation represents a major platelets were negative with the CD36-specific serum FER clinical problem especially in patients with immunization in the platelet suspension immunofluorescence test and the against frequent antigens. Platelet glycoprotein (GP) IV CaptureP assay (Immucor, Ro¨ dermark, Germany) in (=CD36) is expressed in nearly 100% of white Europeans, contrast to CD36-positive control platelets. Whereas FER while 2 to 11 percent of Asian and sub-Sahara African produced positive results in the monoclonal antibody individuals are negative.1–3 CD36 deficiency appears not to immobilization of platelet antigen assay, the patient’s be associated with clinical symptoms. Lack of CD36 can serum did not react with any of three monoclonal present as type I deficiency with neither platelets nor antibodies to CD36 (clone FA6.152 and clone 1A7, monocytes expressing CD36 and type II deficiency with Dianova, Hamburg, Germany and clone 131.4 kindly only platelets lacking GPIV.4 Antibodies to CD36 devel- provided by B Curtis, Milwaukee, WI, USA) in combina- oping afterisoimmunization in type I deficiency can lead to tion with CD36-positive platelets, which may be due to serious complications such as platelet transfusion refrac- steric hindrance. toriness, post transfusion purpura or neonatal alloimmune Aftermobilization chemotherapy,the patient’s platelet thrombocytopenia.5 Here the case of a patient from Oman count recovered spontaneously without further treatment, admitted for HPC transplantation with an aggressive Non- with a peak count of 147 pernl. Autologous hematopoietic Hodgkin’s lymphoma and refractoriness to platelet trans- progenitor cells were successfully harvested and 12.16 Â 106 fusions caused by a GPIV isoantibody is reported. CD34-positive cells per kg body weight were cryopreserved. A 36-year-old patient with diffuse large B-cell lymphoma During workup for high-dose chemotherapy and hemato- and incomplete response to initial chemotherapy and poietic progenitor cell transplantation, a search for CD36- platelet transfusions in Oman came to our medical center negative platelet donors in different internationally operat- in Germany for autologous hematopoietic progenitor cell ing blood centers within Europe and the United States was therapy. No immunization against platelet antigens was unsuccessful. The Japanese Red Cross could have provided reported at that time. He received mobilization chemo- CD36-negative platelets, but the transportation time of 18– therapy with the CD20 antibody rituximab (375 mg/m2 on 24 h could have affected viability and platelet function. No day 1) and ICE (ifosfamide 5000 mg/m2 on day 3, standardized and validated protocol for long-distance carboplatin (area under the curve, 5; capped at 800 mg) transportation was available. Harvest and consecutive on day 3 and etoposide 100 mg/m2 on days 2–4) combina- cryopreservation of autologous platelets of the patient for tion chemotherapy. During aplasia, his platelet count platelet support at time of aplasia is neither an established dropped to 9 per nl and did not increase after infusion of nor a standardized method. Therefore, blood samples of six one pooled random-donor platelet concentrate and three of the patient’s relatives (two siblings, four nephews) living random single-donor apheresis platelet concentrates. Plate- in Oman were shipped to our center for testing, and five let serology included a commercial ELISA assay (GTI- proved to be GPIV-negative. The patient was not condi- PAK; GTI, Brookfield, WI, USA) in two versions tioned until two nephews traveled to Germany and, based (PAKPLUS and PAK12) with purified antigen coated to on a negative platelet crossmatch, served as platelet donors. the plate, the platelet suspension immunofluorescence Conditioning was performed with R-BEAM (rituximab assay, the monoclonal antibody immobilization of platelet 375 mg/m2 on days À8 and À2, carmustine 300 mg/m2 on antigen assay6 and AbScreen HLA class I ELISA (Biotest, day À7, etoposide 200 mg/m2 on days À6toÀ3, cytosine Dreieich, Germany). The patient’s serum was positive with arabinoside 400 mg/m2 on days À6toÀ3 and melphalan glycoprotein IV (GPIV) in the PAKPLUS assay but 140 mg/m2 on day À2), and 12.16 Â 106 CD34-positive cells completely negative in the PAK12 assay, lacking the GPIV perkg of body weight wereinfused on day 0. Platelet count preparation. No HLA class I antibodies were detected. The at that time was 56 pernl. Fromdays þ 4to þ 12 after patient’s serum reacted in the platelet suspension immuno- transplantation, the patient suffered from infectious fluorescence test with 7/7 platelet preparations from complications, with several fever episodes per day, German donors exhibiting reactivities corresponding to although different intravenous antibiotics and voriconazole Letter to the Editor 490 Related platelet GPIV positive Patient donor donor 3 3 3 10 J1 J2 10 K1 K2 10 L1 L2 0.3% 99.6% 102 102 102 101 101 101 CD61PE 100 J3 J4 100 100 L3 L4 K3 K4 0.0% 0.1% 100 101 102 103 100 101 102 103 100 101 102 103 3 3 3 10 B1 B2 10 D1 D2 10 F1 F2 102 102 102 101 101 101 B3 B4 D3 D4 F3 F4 CD14PE 100 100 100 100 101 102 103 100 101 102 103 100 101 102 103 CD36 FITC CD36 FITC CD36 FITC Figure 1 Flow cytometric typing of the platelets (upper row) and monocytes (lower row) of the patient, one of the related platelet donors and a CD36- positive control donor by dual-color staining with the CD36 monoclonal antibody FA6.152 (FITC-conjugated) and anti-CD61 PE (Chemicon, Schwalbach, Germany) or anti-CD14 PE (Beckman Coulter, Krefeld, Germany), respectively. 200 single-nucleotide exchanges to absence of exons 1–3.5,7 In 180 ourpatient, exons 1–14 could be amplified completely by HPC-Tx 160 PCR. Cloning (TA Cloning Kit with vectorpCR2.1; 140 Invitrogen, Paisley, UK) and sequencing (ABI 3730 XL; 120 GPIV negative Random donor platelets PE Applied Biosystems, Weiterstadt, Germany) of the 14 100 platelets exons from genomic DNA showed no variation of the 80 Platelets/nl patient DNA compared to DNA of a GPIV-positive 60 40 control donor and sequences from the National Center for Biotechnology Information databases. Therefore, var- 20 R-ICE Conditioning 0 iations of the genomic DNA cannot serve as an explanation –70 –60 –50 –40 –30 –20 –100 10 20 30 for the GPIV type I deficiency in this patient and regulatory Days prior/post HPC-Tx or transcriptional factors are more likely. Figure 2 Follow-up of the patient’s platelet counts. This case of CD36 deficiency in a patient with non-Hodgkin’s lymphoma demonstrated that immunophe- as anti-fungal medication were administered. In addition, notyping may be a useful and rapid diagnostic tool the patient had severe mucositis, and needed parental when specific antisera or monoclonal antibodies are nutrition and intravenous morphine. During this episode, available. the patient was transfused with nine platelet apheresis units Patients with an ethnic background different from the over10 days, donated by his two relativesto maintain a majority of blood donors from the respective region may platelet count X10 pernl. The platelet count remained cause major problems in blood product supply if they are stable between 13 and 25 pernl on days þ 3to þ 13 after immunized to blood groups with a nearly 100% prevalence. transplantation without bleeding complications (Figure 2). Searching for antigen-negative relatives can be successful, Although a classic 1-h post-platelet transfusion increment as demonstrated in this case. However, increasing migra- measurement was not available, a 5-h post-platelet tion and world-wide medical travel will make problems of transfusion increment, from 16 to 25 per nl and from 13 blood supply more frequent. Strategies to manage these to 22 pernl, was documented twice duringthat time. problems including recruitment of blood donors from Engraftment of white blood cells was observed on day þ 10 ethnic minorities and establishment of standardized and after transplant, and the platelet count recovered to 148 per reliable conditions of transportation for platelets over long nl on day þ 19 without further platelet support. distances from countries with a higher prevalence of CD36 The molecularbackgroundof CD36 type I deficiency has deficiency are necessary. Furthermore, laboratory diagnosis been described for some individuals and ranged from of platelet antibodies must take into consideration the Bone Marrow Transplantation Letter to the Editor 491 ethnic background and possible antigen composition of the its roles in adherence, signal transduction, and transfusion patient before starting elective chemotherapy. medicine. Blood 1992; 80: 1105–1115. 3 Kiefel V, Kroll H, Bonnert J, Unkelbach K, Katzmann B, 1 1 2 3 B Flesch , J Miller , R Repp , S Ott , Nebenfu¨ hrer Z et al. Platelet alloantigen frequencies B Gahn2, N Schub2, M Gramatzki2 and A Humpe2 in Caucasians: a serological study. Transfus Med 1993; 3: 1Institute of Transfusion Medicine, University Hospital 237–242. Schleswig-Holstein, Campus Kiel, Kiel, Germany; 4 Yamamoto N, Akamatsu N, Sakuraba H, Yamazaki H, 2Section of Stem Cell Transplantation and Immunotherapy, Tanoue K.