Immune Thrombocytopenic Purpura after Autologous Haematopoietic Stem Cell Transplantation: Review of the Literature.
Authors: Esther Ana , Canales Miguel Angel , Hernandez-Navarro Fernando 
Published: October 2019

BACKGROUND: A review of autoimmune(AI)events(AIE) post- autologus stem cell transplantation(ASCT) has recently been published(Daikeler T et al, 2007) but there are few papers about treatment and outcome of AI thrombocytopenia(IT) due to the low frequency and short follow-up.We have reviewed reported cases of IT because the mechanisms are multiple and poorly understood.

METHOD: Patients(29p)had been diagnosed with leukaemia 13p, MM 2p, NHL 10p, MSD 1p or solid tumours 3p.Several transplantation variables have been analysed to find any clinical features related to higher risk of IT. Response to treatment and clinical follow-up have been studied, too.

RESULTS: There was no direct relation between gender(58.62% female);age(38,83; range 16–58);WBC(5,68x109/l; range1–19) or source and IT(63x109/l; range:1–279).Contrary to reported cases, fludarabine(FLUD),total body irradiation(ITB) administered as conditioning(13,8%)/mobilization regimen (37,8%) or rhG-CSF treatment(2 p) were not associated to AIE. However, the study has important limitations like FLUD was administered in only 3p and mobilization treatment was similar in all cases(Table).IT was resolved in all patients and recurred in only 1p early since steroid(CE) treatment had been stopped.Treatment was not necessary in 2p.The period between transplant and thrombocytopenia was 23.1 months(range 1–80) so aplasia alone can not explain it and it is obligatory to investigate the role of immune deregulation.Steroid, IVIg, Danazol or monoclonal antibody(Rituximab) are possible treatments.

DISCUSSION: Different hypothesis have tried to explain postransplant AIE and most authors conclude that the modification of self-antigens expression or its combining with forming “altered self” antigens might contribute.The radio-chemotherapy damage thymic function and deplete T cells(CD8/CD4) while expanding B cells. However, the mechanism of clonal proliferation of B cell remains unclear.Furthermore, the breakdown of tolerance and delayed(≤6 months) recovery of regulatory T cells after some drugs like FLUD have not been properly explored yet.The bone marrow biopsy is an obligatory diagnosic tool for distinguish between delayed recovery and ITP. However, the anti platelet IgG test is not a major diagnostic criterion(pos 13/26 of total IT) because CE have been usually administered previously. It has positive predictive value(VPP) 46% and VPN 82%. The favourable response of AIE to therapy might support the role of graft-versus-host disease after ASCT.

CONCLUSION: Although IT is more unusual, it should be considered in the differential diagnosis of post-transplant thrombocytopenia. Its relationship with antitumoral effect and post-transplant immune reconstitution should be considered for growing development of immunotherapy.

Drugs received prior to ASCT in the 29 reported cases. QT N°cases % QT N°cases % Az: Azathioprine;BM: bleomycin; Bu: busulfan; Bz: bortezomid; CLB: chlorambucil; CTX: cyclophosphamide;DXT: dexamethasone; DOX: doxorubicin; Etop: etoposide;IDA: Idarrubicina; IFOS: Ifosfamide; Melph: melphalan; MTX: methotrexate; MTZ: mitoxantrone;6TG: 6-thioguanine; VLB: vinblastine; VCR: vincristine.*QT schedule Bz 2 6,9 VCR 5 17,2 PROMACE* 2 6,9 CE 4 13,8 VLB 2 6,9 m-AMSA 4 13,8 BM 2 6,9 MTZ 4 13,8 MTX 3 10,3 AZA 2 6,9 IFOS 4 13,8 Melp 2 6,9 ACVBP* 4 13,8 Ranimustina 2 6,9 BEAM* 3 10,3 DXT 3 10,3 Cisplatin 3 10,3 Thiotepa 2 6,9 CTX 10 34,5 Carboplatin 2 6,9 BCNU 2 6,9 FLUD 3 10,3 Etop 11 37,9 CHOP* 4 13,8 Bu 2 6,9 TBI 4 13,8 DOX 10 34,5 CLB 2 6,9 ARA-C 12 41,4 NA 6 20,7 6TGN 7 24,1