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  • Graft versus host disease prophylaxis included tacrolimus

    2019-04-15

    Graft versus host disease prophylaxis included tacrolimus, mycophenolate mofetil and post transplant cyclophosfamide (50mg/kg on days +3 and +4) as previously proposed by Baltimora׳s group. After a follow up of 18 months patient is in good clinical conditions, in persisting complete remission as established both by PET and CT scan. Moreover the TCR αβ molecular analysis shows an oligoclonal pattern fully distinct from which manifested during the disease (Fig. 2).
    Discussion We started with a CHOP regimen but after the first Ubenimex we had to shift the therapeutic approach towards a salvage regimen. We administered four cycles of hyper-C-HiDAM protocol, a therapeutic scheme containing hyperfractionated cyclophosphamide plus high-doses of Ara-C and methotrexate [10] followed by autoSCT. This approach is reported being effective for patients with aggressive NHL refractory to first-line anthracycline-containing regimens. A partial remission was obtained at the end of the program. However, as previously reported in PTCL [11,12], only the achievement of complete remission after induction therapy is a strong predictor of long term survival; thus, in this category of patients with a high risk of disease recurrence the general recommendation is to proceed rapidly to an allogeneic transplant. Unfortunately the major problem is related to the aggressiveness of the underlying disease, that does not allow to have enough time to find a suitable donor and to proceed to transplantation. Historically, alloSCT from HLA-haploidentical relatives has been limited by an unacceptably high non-relapse mortality, due to high rates of graft rejection and GVHD [13]. T-cell depletion of the donor graft represented a step forward in the haplo setting, but it required a high level of expertise in laboratory techniques [14]. Recently, the Baltimora and Seattle groups have pioneered a method to selectively deplete alloreactive cells in vivo by administering high doses of cyclophosphamide immediately post haplo-transplant (PT/Cy) after a nonmyeloablative conditioning regimen. This approach resulted in a very low NRM, due to low incidences of GVHD and infectious complications [15]. In the previous years several studies [16–18] have confirmed the encouraging results of the haploidentical PT/Cy strategy. This alternative source with haploidentical donor is growing as a valid alternative option if a matched related donor is not rapidly available. At the beginning our strategy was to follow the Baltimora׳s original scheme; however, given the very fast disease progression, we decided to change the type of pre-transplant conditioning therapy. We chose a myeloablative regimen with Thiotepa, Bufulsano and Fludarabine, in an attempt to achieve a better disease control in a patient with a well established refractory malignancy [19]. Allogeneic transplantation with myeloablative conditioning in peripheral T-cell lymphoma is a potentially curative option [20], but it is associated with a high treatment-related mortality (TRM), in particular after a failed autoSCT [21].Our patient at the time of transplant was in a relatively young age, in good clinical conditions, and without significative comorbidities (Sorror score 0), despite disease progression and previous treatment. Finally, as previously reported [22] in other subtypes of peripheral T cell lymphomas, the persistence of complete remission after allografting corroborates the perception that a graft-versus-T cell lymphoma effect may play a role in the curative potential of alloSCT.
    Conflict of interest