scholarly journals Total Marrow Irradiation for Second Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Alida Dominietto ◽  
Stefano Vagge ◽  
Susanta Hui ◽  
Carmen Di Grazia ◽  
Teresa Lamparelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Leukemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Total Marrow Irradiation ◽  
Alpha Beta

Background. Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is associated with very poor outcomes. A myeloablative conditioning regimen for patients with advanced acute leukemia before second allogeneic HSCT is crucial to better control the disease, but the risk of transplant mortality due to toxic complications is very high. Total Marrow Irradiation (TMI) is a novel high precision radiation treatment, alternative to standard Total Body Irradiation (TBI) conditioning regimen, allows to deliver therapeutic radiation doses over extensive selected targets while substantially reducing radiation to vital organs to preserve their functions. Aim of the pilot study. To evaluate the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine and alkeran as conditioning regimen in 9 patients with acute leukemia relapsed after a first allogeneic HSCT. Patients and Methods. Nine patients relapsed after first allogeneic HSCT received a second allogeneic HSCT, 7 from haploidentical, 1 from unrelated (UD) 10/10 and 1 from HLA-identical sibling (SIB) donor. The conditioning regimen consisted of: TMI 8 Gy in 5 patients on day -8 -7 or TMI 12 Gy in 4 patients on day -9 -8 -7, plus Thiotepa 5 mg/Kg on day -6, Fludarabine 50 mg/mq on day -5 -4 -3, alkeran 140 mg/mq on day -2. TMI was delivered in daily single fraction dose of 4 Gy, instead of the conventional 2 Gy in order to potentially enhance the biological effective dose approximately 20% to 60% (for a total dose of 12 Gy), considering alpha/beta ratio between 10-1.49, while total dose of 8 Gy in 2 fractions schedule is potentially equivalent to six fractions of conventional TBI for low alpha/beta ratio. Graft versus host disease (GvHD) prophylaxis for SIB and UD consisted of cyclosporine methotrexate and ATG, whereas for HAPLO it was high dose post-transplant cyclophosphamide (PT-CY), cyclosporine and mycophenolate. The median age was 45 years (range, 19-70 years); 3 patients were in remission, 6 had active disease at the time of the second allogeneic HSCT. The median number of nucleated cells infused was 4.3 x 10e8/Kg (range 2.6-7.7). Four patients received peripheral blood and 5 patients received unmanipulated bone marrow cells. Results. The median time to neutrophil counts of > 0.5 x 10e9/L was 16 days (range 13-22) and to platelet counts of > 20 x 10e9/L was 19 days (range 11-27) respectively. All the patients showed a full donor chimerism on day 30 after transplant; none of the patients had rejection. Three patients developed acute graft versus-host disease (aGvHD) grade I-II and 1 patient had moderate chronic GvHD. During the neutropenic phase of the transplant one patient developed a sepsis from Pseudomonas Aeruginosa; one patient had pericardial effusion and one patient had mucositis grade II. The median follow up was 528 days (range 227-858). Day +30 and day +100 transplant related mortality were 0. Two patients died of transplant related complications; both died of interstitial pneumonia and received TMI 12 Gy. Two patients died of leukemia and they were not in remission at the time of the transplant. The actuarial 17 months disease free-survival (DFS) is 53%. Conclusions. This is the first report demonstrating the safety and the efficacy of the TMI conditioning regimen in patients with advanced acute leukemia receiving second allogeneic transplantation with encouraging outcome in terms of engraftment, early toxocity, GvHD and relapse. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chronic-graft-versus-host-disease-related polymyositis: a 17-months-old child with a rare and late complication of haematopoietic stem cell transplantation.

2020 ◽  
Vol 12 (1) ◽  
pp. e2020002
Author(s):  
Matteo Chinello ◽  
Rita Balter ◽  
Massimiliano De Bortoli ◽  
Virginia Vitale ◽  
Ada Zaccaron ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host

Background: Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. Case report: We report a case of a 17-months-old child affected by hemophagocytic lymphohistiocytosis who underwent a matched unrelated donor haematopoietic stem cell transplantation (HSCT). She developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. Conclusions: This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.

Clonal T Cell Large Granular Lymphocyte Leukaemia of Recipient Origin after Related Mismatched Allogeneic Haematopoietic Stem Cell Transplantation for Acute Myeloid Leukaemia as a Possible Consequence of Anti-Thymocyte Globulin in Conditioning Regimen

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4312-4312
Author(s):  
Loïc Fouillard ◽  
Christophe Marzac ◽  
Monique Lagrange ◽  
Stéphanie Huguet-Jacquot ◽  
Betina Fabiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Acute Myeloid Leukaemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Abstract Polyclonal or oligoclonal expansion of T cell large granular lymphocyte (T-LGL) after allogeneic haematopoietic stem cell transplantation (HSCT) has been described. A few cases of clonal T-LGL leukaemia of donor origin has been reported as a post transplantation lymphoproliferative disorder (PTLD) and described after allogeneic HSCT (Chang, Am J Clin Pathol, 2005). We report here a patient with a clonal T-LGL of recipient origin occurring after allogeneic HSCT for acute myeloid leukaemia (AML). A 56 year old male patient with an AML received an HLA mismatched (disparity on locus A) related HSCT from his sister in first complete remission. Conditioning regimen was myeloablative and combined Busilvex (12.8 mg/kg) and Cyclophosphomide (120 mg/kg) (BuCy2). Anti-Thymocyte Globulin (ATG Sangstat) was added because of the HLA disparity between donor and recipient at a dose of 15 mg/kg. Prophylaxis of Graft versus Host Disease (GVHD) combined cyclosporine and methotrexate. Complete engraftment was observed with full haematopoietic recovery and 100% donor type chimerism detected by real time quantitative PCR (RQ-PCR). A grade II acute GVHD resolved under steroid and CMV infection was treated with valganciclovir. Ten months post HSCT while all immunosuppressive treatment was discontinued, a severe neutropenia (poly morpho nuclear <0.2 × 109/l) and an hyperlymphocytosis up to 10×109/l occurred with a thrombocytopenia of 100×109/l. Relapse of AML and viral infection (CMV, HHV6, EBV, HCV, HBV, HIV, HTLV1, parvovirus B19) were eliminated. Seach for autoantibodies was negative. No chronic GVHD was diagnosed. The predominant cells in blood films were typical LGLs. Flow cytometric analysis showed a population CD3+/CD8+/CD57+/CD56− consistent with T-LGL. Bone marrow biopsy confirmed agranulocytosis and T-LGL infiltration CD3+/CD8+/CD57+/CD56−. Secondarily agranulocytosis and thrombocytopenia spontaneously resolved within one month, but hyperlymphocytosis persisted with the same T-LGL profile. Chimerism by RQ-PCR on CD3+ and CD3− peripheral blood mononuclear cells (PBMNC) population at time of profound agranulocytosis revealed that donor cells were only 8.2 % and 1.2% on CD3+ and CD3− fractions respectively. Chimerism done when cytopenia resolved became mixed with 47% and 39% donor markers on CD3+ and CD3− fractions respectively. Chimerism was then performed on selected subpopulations; donor markers were 98% on CD14+/15+ myeloid cells, 100% on CD56+ natural killer (NK) cells and 78 % on CD19+ B cells. Cell sorting isolated two T-LGL subpopulations according to CD57 expression: CD57+bright and CD57+weak. Donor markers were 0.02% on CD3+/CD8+/CD57+bright T-LGL cells and 1.2% on CD3+/CD8+/CD57+weak T-LGL cells. These results were in favor of a recipient origin of the T-LGL population without loss of the graft. The diagnosis of clonal T-LGL population was confirmed by TCRg gene rearrangement performed on the selected CD3+/CD8+/CD57+bright and CD3+/CD8+/CD57+weak population. In addition a polyclonal background was observed only in the CD3+/CD8+/CD57+weak population. These data show that T-LGL leukaemia of recipient origin can occur after allogeneic HSCT for AML and can be included as a PTLD. The role of ATG as an intensive immunosuppressive treatment cannot be excluded in the occurrence of this PTLD. In this patient no treatment of T-LGL leukaemia and a wait and watch attitude were undertaken. Eighteen months post HSCT the patient is alive and well with the same stable PTLD profile and no relapse of AML The cytolytic activity of the recipient T-LGL clone could explained the absence of AML relapse and a transient toxicity against donor haematopoiesis. In vitro cytolytic assay will be done to confirm the cytotoxic activity of T-LGL against leukaemic cells and haematopoietic stem cells.

Problem-solving in clinical practice: breathing difficulty and muscle weakness following allogeneic haematopoietic stem cell transplantation

2020 ◽  
pp. edpract-2019-317281
Author(s):  
Bashaer Albulushi ◽  
Farah Thabet ◽  
Saad Alshahwan ◽  
Yasser Elborai ◽  
Nawaf Alkhayat ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Stem Cell ◽  
Clinical Practice ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Neurological Manifestations ◽  
Allogeneic Hsct ◽  
Graft Versus Host

Acute weakness and dyspnoea are unusual presentation after allogeneic haematopoietic stem cell transplantation (HSCT) complicated by chronic graft-versus-host disease (GVHD). The differential diagnosis and management are challenging for the paediatrician. This case chronicles the diagnostic journey of a child who presented with weakness, dyspnoea and difficulty in speech, 2 years after allogeneic HSCT and GVHD and explores the approach to neurological manifestations in this context.

scholarly journals Study protocol of a pilot study evaluating feasibility and acceptability of a psychosexual intervention for couples postallogeneic haematopoietic stem cell transplantation

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039300
Author(s):  
Brindha Pillay ◽  
Maria Ftanou ◽  
David Ritchie ◽  
Yvonne Panek-Hudson ◽  
Michael Jefford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Sexual Dysfunction ◽  
Stem Cell Transplantation ◽  
Relationship Satisfaction ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Post Transplantation ◽  
Allogeneic Hsct

IntroductionSexual dysfunction is one of the most common side effects of allogeneic haematopoietic stem cell transplantation (HSCT) for haematological cancers. Problems can persist between 5 and 10 years post-transplant and impact mood, couple intimacy and relationship satisfaction. Few intervention studies, however, target sexual dysfunction in patients post-HSCT. This pilot study aims to examine the feasibility and acceptability of implementing a psychosexual intervention for HSCT survivors and their partners post-transplantation.Methods and analysisFifteen allogeneic HSCT survivors and their partners will be recruited. Patients who are more than 3 months post-transplantation will be sent invitation letters describing the couples’ psychosexual intervention that will be offered through this study. The intervention will comprise two components: (1) psychosexual education about medical and behavioural treatment options for sexual dysfunction delivered by a haematology nurse consultant; (2) emotionally focused therapy-based relationship education programme for couples delivered by a clinical psychologist (four sessions of 1.5 hours each). Couples who consent to participate will be administered a series of measures assessing mood, relationship satisfaction and sexual dysfunction preintervention and post-intervention, as well as satisfaction with the intervention postintervention. Feasibility of the intervention will be examined via recording enrolment rate, adherence, compliance with completing outcome measures and fidelity of intervention delivery.Ethics and disseminationEthics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national and international conferences and published in a peer-reviewed journal so that in can be accessed by clinicians involved in the care of allogeneic HSCT patients. If this intervention is found to be feasible and acceptable, its impact will be examined in a future randomised controlled trial and subsequently implemented as part of routine care in the allogeneic HSCT population.

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