Relapsed Follicular Lymphoma and Haploidentical Transplantation Using Double Source of Hematopoietic Stem Cells and Post-Transplant Cyclophosphamide: Case Report
Authors: Fonseca Ana Rojas , Hamerschlak Nelson , Oliveira José Salvador Rodrigues de 
Published: November 2019

Follicular lymphoma (FL) is a heterogeneous disease with varying prognosis owing to differences in clinical, laboratory, and disease parameters. Although FL is considered incurable disease with standard chemotherapy, advances in treatment have improved disease its management and clinical outcomes. Treatment for relapsed or refractory patients is influenced by initial first-line therapy and the duration and quality of the response. Presently, there is no consensus for treatment of patients with early or multiple relapsed disease; however, numerous drugs, combination regimens, and transplant options have demonstrated efficacy. Considering that there is no consensus to treat such patients, we are reporting this case.
A 37-yo woman presented in Sep 2005 with abdominal masses, constitutional symptoms and two years of recurrence of urinary and pelvic infections, with previous lymph nodes biopsies revealing hiperplasia. At this time grade I FL, stage IVB, with bone marrow involved was done. There was no response to four cycles of Rituximab and three of COP. In Jan 2006 a histological review confirmed the diagnosis. Then she underwent to six cycles of R-CHOP 21, resulting in complete remission (CR) was ruled out. Consolidation therapy consisted to IL-2 monthly four cycles, and an eight quarterly Rituximab for two years. Supportive care with polyclonal immunoglobuline infusion monthly was demanded to overcome frequent urinary and respiratory infections.
After nine years, Dec 2015, constitutional symptoms returned and PET/CT was positive in mediastinum and there was bone marrow involvement. From Jan to Jun 2016, 6 cycles of Rituximab and Chlorambucil was done, and after the second one she complicated with pulmonary aspergillosis and there underwent voriconazole for 18 months. In Jul and Nov 2016 PET/CT revealed a second CR. Just four months later, BMB and pulmonary infiltrated disclosed a new relapse. Four cycles of Fludarabine 30 mg/m², Mitoxantrone 8 mg/m², Rituximab 375 mg/m² and dexamethasone were attempted, since Apr to Jul 2017. A fosfomycin therapy was done to prevent a recurrence of Escherichia coli multi-resistant urinary tract infections. The patient achieved a third CR at PET/CT in Aug 2017.
Based on the last rapidly progression of the disease, and bone marrow involvement in all relapses, we proposed an allogeneic stem cell transplantation (allo-SCT). But she didn't have a match related donor. So, her twelve years old son was considered as an haploidentical donor. A reduced intensity conditioning (RIC) was performed with Cyclophosphamide 14.5 mg/Kg D-6 and D-5, Fludarabine 30 mg/m² D-6 to D-3, TBI 200 cGy at D-1. A double source of stem cells: primed-bone marrow (TNC 4.49 x 10⁸/Kg) plus peripheral blood stem cell (4.48 x 10⁶ CD34+/Kg) was infused on Oct-10-2017. Immunosuppressive therapy consisted of Cyclophosphamide 50 mg/Kg at D+3 and D+4 (PT-Cy), Tacrolimus and MMF starting at D+5, and G-CSF from D+5 until neutrophil engraftment. The neutrophil engraftment reached at D+14.
Cytokine Releasing Syndrome, febrile neutropenia, rectal prolapse and grade I/II acute graft versus host disease (aGvHD) were immediate complications. Discharge occurred at day +18. CMV PCR positive was preemptive treated from Nov to Dec 2017. Steroid therapy was given for grade II aGvHD, Nov 2017 till Dec 2018. She had an Orthostatic Tachycardia Syndrome from Feb to Oct 2018; Respiratory Syncytial Virus, from Jul to Aug 2018; Rhino and B Influenza upper airway infection on Mar 2019. A complete chimerism was achieve at +100, +180 and +365 days. PET/CT confirmed CR at D+180 and +365.
At the present she is off treatment since Jan 2019. In this situation a double source haplo-SCT was a successfully therapy overcame the complicated comorbidities before transplantation, with a good quality of life nowadays.

Disclosures
No relevant conflicts of interest to declare.