scholarly journals IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

2016 ◽  
Vol 8 ◽  
pp. 2016057 ◽  
Author(s):  
Franco Aversa ◽  
Lucia Prezioso ◽  
Ilenia Manfra ◽  
Federica Galaverna ◽  
Angelica Spolzino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Post Transplant

The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC)   showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

Haploidentical Hematopoietic Stem Cell Transplantation in Children Leukemia and Lymphoma with G-CSF Mobilized Marrow Grafts without T Cell Depletion: A Single Center Report of 45 Cases.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3282-3282
Author(s):  
HengXiang Wang ◽  
Hong-Min Yan ◽  
Lian-Ning Duan ◽  
Ling Zhu ◽  
Mei Xue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Hematopoietic Malignancies

Abstract Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) has been increasingly used in the treatment of patients with hematopoietic malignancies without immediate HLA-matched donors. Here, we describe a protocol for the management of hematopoietic malignances in children and adolescents who received T cell replete G-CSF-mobilized bone marrow grafts from HLA-mismatched parents. The donors were administered G-CSF for 7 consecutive days before marrow grafts containing a medium nucleated cells of 8.1×108/kg (range: 6.1–11.5×108/kg) were collected. 45 patients were pre-conditioned with high-doses of cytarabine and cyclophosphamide plus total body irradiation or BU for chronic myeloid leukemia patients. The regimen for acute graft versus host disease (aGvHD) prophylaxis included antithymocyte globulin, monoclonal antibody against CD25 (Simulect), CsA, MTX and mycophenolate mofetil. Three of forty-five patients died of engraftment failure, multiple organ failure and TTP, others achieved complete donor chimerism with the medium days for neutrophil (>0.5′109/L) and platelet recovery (>20′109/L) were 17(12–23 days) and 19(12–27days). Of the 42 evaluable patients, 3 cases developed grade III/IV aGvHD, and 9 of 32 cases who survived longer than 3 months developed chronic GvHD. Twenty-one patients died within a medium follow-up of 36 months(24–63 months), including 2 of transplantation related death, 11 of leukemia relapse, 4 of CMV and fungal infections, and 2 of aGvHD and 2 cases died of other reasons. The disease-free survival rate was 53%. Multivariate analysis demonstrated that the overall survival was not significantly reduced in refractory leukemia and seemed not associated with the mismatch numbers of HLA loci. These results indicate that T cell replete SCT with mobilized bone marrow from HLA-2 or -3-antigen mismatched parents could be an optional strategy for children with hematopoietic malignancies who lack immediate access to a HLA-matched stem cell source.

Allogeneic hematopoietic stem cell transplantation for cutaneous T-cell lymphoma (CTCL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7540-7540
Author(s):  
C. Hosing ◽  
M. Donato ◽  
I. F. Khouri ◽  
D. T. Chu ◽  
D. L. Bethancourt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Treatment Regimens

7540 Background: Patients (pts.) with advanced CTCL have a poor prognosis. There has been limited experience with the use of allogeneic hematopoietic stem cell transplantation (HSCT) in these pts. We report the results of 11 pts. with advanced CTCL/Sezary syndrome who underwent allogeneic HSCT at our institution. Patients and Methods: All pts. signed informed consent. Median age at the time of HSCT was 50.5 years (range, 22–63). There were 8 F/3M. All were diagnosed with stage IV disease. The median number of prior treatment regimens was 5.5 (range, 3–11). Treatment regimens included PUVA, TSEB, ECP, topical therapy, retinoids, bexarotene, denileukin diftitox, and multiagent chemotherapy. Seven pts. had a PR to treatment administered prior to transplantation, 2 pts. were in CRu and 2 pts. had SD. The conditioning regimen was fludarabine (125 mg/m2), melphalan 140 mg/m2 in 8 pts., fludarabine (125 mg/m2), cyclophosphamide (3 g/m2) ± rituximab in 2 pts., and fludarabine (120 mg/m2), busulfan (11.2 mg/m2) in 1 pt. Patients who received unrelated or mismatched related stem cells also received ATG. GVHD prophylaxis was with tacrolimus/methotrexate in all patients. Results: Ten of 11 pts. engrafted with a median time to ANC >500 mm3 of 12 days (range, 8–14). One pt. died at 17 days post transplant without engraftment due to sepsis. One pt. developed autologous reconstitution and underwent a 2nd allogeneic HSCT procedure and remains in CR at 3 years post transplant. Of the remaining 9 pts., 7 achieved full donor chimerism and 2 pts. were mixed chimera. At the time of this report 4 of 11 pts. have died. Cause of death was sepsis in 2, fungal pneumonia in 1, and PD in 1 pt. Three pts. relapsed post transplant, all 3 were induced back in to a CR by tapering of immunosuppression (2) or DLI (1). Overall 7 pts. continue to be alive and remission with a median follow up of 2.9 years (range, 3 months to 4.4 years). Four of 7 pts. have cGVHD requiring treatment (Table). Conclusions: Allogeneic HSCT is an effective therapy for refractory CTCL/SS and merits further evaluation. [Table: see text] No significant financial relationships to disclose.

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