scholarly journals Bone Marrow Compared with Peripheral Blood Stem Cells for Haploidentical Transplantation with a Nonmyeloablative Conditioning Regimen and Post-transplantation Cyclophosphamide

2014 ◽  
Vol 20 (5) ◽  
pp. 724-729 ◽  
Author(s):  
Luca Castagna ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Stefania Bramanti ◽  
Jean El Cheikh ◽  
...  
Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5527-5527
Author(s):  
Benakli Malek ◽  
Ahmed Nacer Redhouane ◽  
Bouarab Hanane ◽  
Baazizi Mounira ◽  
Zerkout Sara ◽  
...  

Abstract Introduction: allogeneic haploidentical identical stem cells transplantation (SCT) is currently a salvage procedure in patients with hematologic malignancies at high risk and who have no HLA identical donor. The new modalities of haploidentical transplantation without in vitro T depletion of the donor, seem to allow rapid immune reconstitution and reduce the incidence of graft versus host disease (GVHD). This retrospective study presents the short-term results of this procedure in a single-center series, using a unmanipulated graft involving both bone marrow and peripheral blood stem cells after exposure to G-CSF donor. Material and Methods: From May 2013 to March 2015, 15 allografts SCT HLA-haploidentical were used in 14 pts with hematological malignancies (3 AML, 9 ALL, one acute CML and one lymphoblastic NHL). The median age is 24 years with a sex ratio of 2,5. Median time diagnosis-transplant is 27 months (2-74). At the time of transplant, 8 pts were in second complete remission and 3 pts in blast phase. The donor used was one of the two ascendants (father: 5, mother: 2) or sibling (brother: 5, sister: 3), median donors age 38 years (17-65). The degree of compatibility (HLA A, B and DR) is 3/6 (8 cases), 4/6 (6 cases) and 5/6 (1 case). CMV status between donor/recipient was high risk in 14 cases. ABO incompatibility is major in 3 cases, minor in 4 cases. The conditioning regimen associated Busilvex 9.6 mg/kg; Aracytine 8 g/m2; Endoxan 3.6 g/m2. The prevention of GVHD involved the Cyclosporine-Methotrexate association, MMF and Thymoglobulin 10 mg/kg. All pts received an association of bone marrow transplant and peripheral blood stem cells (from the donor receiving first G-CSF at a dose of 5 μg/kg) with a total average rate of NC: 8,9.108/kg , CD34: 11.29 106/kg (1,43-18,25), MNC: 8,9.108/kg (4.80-17.97), CD3: 3,61 108/kg (0.04-14), CD4: 1.36 108/kg (0,02-7.53), CD8: 1.24 108 (0,36-7.53). A second haploidentical allogeneic transplantation (from another donor) with Fluadarabine-Melphalan conditioning, was required in a pt who presented early rejection. Results: aplasia was observed in all pts with average duration of 21 days (15-21). The output is seen aplasia average J17 (12-23). No cases of VOD was observed. One pt presented an early rejection and received a second haploidentical transplantation. Acute GVHD occurred in 9 pts (64.2%) including 8 (57%) of grade II-IV; a chronic GVHD in 2 pts (18%) of extensive form. Seven pts (46%) developed CMV reactivation occurred in average d44 (35-67). Three cases of hemorrhagic cystitis (one grade 4) are observed on average d47 (30-75). Three pts (21%) relapsed four months after transplantation (all in blast phases at the time of graft). After a median follow-up of 11 months (4-25), 8 pts (58%) are alive and 6 pts (42%) died (digestive aGVH: 1, severe infection: 2, hemorrhagic cystitis: 1, relapse: 2). The actuarial overall survival and event-free survival at 28 months are 42.4% and 37.5% respectively. Conclusion: The results of the allogeneic SCT using unmanipulated haploidentical from the marrow and peripheral blood, after a myeloablative conditioning, seem encouraging in pts with hematological malignancies at advanced stages. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 18 (2) ◽  
pp. 43-52
Author(s):  
A. E. Burya ◽  
K. I. Kirgizov ◽  
E. A. Pristanskova ◽  
M. B. Melnikova ◽  
V. V. Palm ◽  
...  

Generalized osteopetrosis is a rare hereditary disease characterized by impairment of skeleton bones formation, bone marrow dysfunction, neurologic deficiency and blindness. The main treatment for osteopetrosis is an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To review and analyze experience of Department of bone marrow transplantation of RDKB (BMT RDKB) of allo-HSCT for patients with autosomal recessive generalized osteopetrosis; to evaluate tolerability and efficacy of the conditioning regiment administered. Between 2010 to 2018 years, 7 patients (2-male, 5-female) with autosomal recessive generalized osteopetrosis underwent allo-HSCT in tDepartment of bone marrow transplantation of RDKB. Median age at the moment of HSCT was 5,5 years (1–11 years). Before the transplantation myeloablative conditioning regimen was used: treosulfan, fludarabine and melphalan for 5 patients, treosulfan, fludarabine and thiotepa for 1 patient and treosulfan with fludarabine for 1 patient. In case of unrelated allo-HSCT antithymocyte globulin was added to the conditioning regimen. Bone marrow from matched (HLA- 10/10) unrelated donor was used for 4 patients, peripheral blood stem cells from matched unrelated donor was used for 1 patient, two grafts of unrelated umbilical cord blood (HLA 8/10 and 9/10) for 1 patient and peripheral blood stem cells from matched (HLA 10/10) from related donor – for 1 patient. For “graft-versus-host” disease (GVHD) prophylaxis either cyclosporine A/tacrolimus and methotrexate/ mofetil mycophenolate was used. White blood cell recovery had been achieved for 6 from 7 patients on +13 to +22 day (median +17 day). Quick autoreconstitution of hemopoesis was observed for the recipient of umbilical cord blood who got one myeloablative drug. The following early post transplantation complications were registered: oropharyngeal mucositis up to II degree in 6 patients, neutropenic enterocolitis up to II degree in 4 patients, up to III degree in 3 patients, sepsis in 3 patients. The GVHD symptoms occurred in 2 cases: skin form of II degree in one patient and skin form of II degree and intestinal form of IV degree in another patient. One patient with neurodegenerative form of osteopetrosis died with increase of hypertensive-hydrocephalus syndrome, cerebral edema with downward cerebellar herniation. During 5-6 months after allo-HSCT the 5 successfully transplanted patients experienced poor graft function but then reduction of extramedullary hemopoesis occurred and full engraftment was achieved. Hypercalcemia was reported in 2–5 months after allo-HSCT and was treated by administration of bisphosphonates. Visual impairment persisted after allo-HSCT. After 4–6 months after transplantation axis skeleton growth occurred for all 5 successfully transplanted patients, skull deformation reduced and no new zones of nerve’s compression were observed. No patients had any developmental delays after the treatment. Allo-HSCT is an effective systemic treatment of autosomal recessive generalized osteopetrosis. However because serious neurodegenerative condition cannot be reversed by allo-HSCT, such treatment may not be recommended for patients with heavy CNS impairment. Myeloablative conditioning regimen with two alkylating agents provides allogeneic reconstitution of hemopoesis. In post transplantation period, measures for hypercalcemia control are necessary. Early diagnostic of autosomal recessive generalized osteopetrosis can help to evaluate feasibility of allo-HSCT and to start treatment on time thus provide chance for long-term rehabilitation and prevention of serious disability. The study was approved by the Independent Ethics Committee of Russian Children's Clinical Hospital.


1994 ◽  
Vol 3 (2) ◽  
pp. 135-139
Author(s):  
ALISON RICE ◽  
JEAN-MICHEL BOIRON ◽  
CAROLINE BARBOT ◽  
MARYSE DUPOUY ◽  
NADINE DUBSOC-MARCHENAY ◽  
...  

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