Genetic Basis of Donor–Recipient Matching in Allogeneic Transplantation of Hematopoietic Stem Cells

Author(s):  
Jacek Nowak ◽  
Jacek Wachowiak
2011 ◽  
Vol 11 ◽  
pp. 1068-1076 ◽  
Author(s):  
Gero Hütter ◽  
Susanne Ganepola

Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1–infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hematopoietic stem cells engrafted, proliferated, and differentiated into mature myeloid and lymphoid cells. To date, the patient has not required any antiretroviral treatment, more than 4 years after allogeneic transplantation. In the analysis of peripheral blood cells and different tissue samples, including gut, liver, and brain, no viral load or proviral DNA could be detected. Our report raises the hope for further targeted treatment strategies against HIV and represents a successful personalized treatment with allogeneic stem cells carrying a beneficial gene. However, this case has ignited a controversy regarding the question of whether this patient has achieved complete eradication of HIV or not. Here we give an update on open questions, unsolved aspects, and clinical consequences concerning this unique case.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Stefania Trino ◽  
Pietro Zoppoli ◽  
Angelo Michele Carella ◽  
Ilaria Laurenzana ◽  
Alessandro Weisz ◽  
...  

Transfusion ◽  
2016 ◽  
Vol 56 (9) ◽  
pp. 2331-2335 ◽  
Author(s):  
Mark A. Fiala ◽  
Soo Park ◽  
Michael Slade ◽  
John F. DiPersio ◽  
Keith E. Stockerl‐Goldstein

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2481-2481
Author(s):  
Eucario León-Rodríguez ◽  
Patricia Guzmán-Uribe ◽  
Marcela Deffis Court ◽  
Sandra Ileana Perez-Alvarez ◽  
Monica M Rivera Franco

Abstract Introduction: To date, worldwide, the main source of stem cells is peripheral blood (PBSCs). However, its use has been associated with a higher incidence of graft versus host disease (GVHD) when compared with the use of bone marrow. It has been demonstrated that the fast engraftment using G-CSF-primed bone marrow as a source of stem cells, compares to that seen with PBSCs, and it is also associated with a decreased incidence of GVHD. Objective: To describe the results obtained from allogeneic, G-CSF-primed bone marrow transplantations, at INCMNSZ, from November 1998 to March 2013. Material and methods: A retrospective analysis was performed in patients who underwent allogeneic, G-CSF-primed bone marrow transplantation. Clinical characteristics, frequency of GVHD, and survival, were conducted, using the Statistical Software Package SPSS v21.0. Results: Forty-nine patients who underwent allogeneic, G-CSF-primed bone marrow transplantation, from November 1998 to March 2013, were included. Patients (male, 63%) had a median age of 29 years (range 16-59). The patients had a following range of underlying diseases: aplastic anemia (n=15, 30.6%), myelodysplastic syndrome (n=12, 24.5%), chronic myeloid leukemia (CML, n=9, 18.4%), acute lymphoblastic leukemia (LLA, n=7, 14.3%), acute myeloid leukemia (AML, n=3, 6.1%), or others (n=3, 6.1%). Patients achieved a bilineage engraftment with a median time of 20 days (range, 11-40) for absolute neutrophil count and 15 days (range, 5-45) for platelets. Acute GVHD was observed in 4 patients (8.2%), reported as grade I and II; and 14 patients (28.6%) experienced a limited form of chronic GVHD. Nine out of 49 (18.3%) patients relapsed: CML (n=5), AML (n=1), AA (n=1), ALL (n=1), others (n=1). All patients with relapsed CML were treated with donor lymphocyte infusions, but only 2 responded. Treatment related mortality (TRM) was 8.16%, including infectious complications in 2 patients, cGVHD in one patient, and veno-oclussive disease (VOD) in one patient. Overall mortality was 26.5%; the majority of deaths (69.2%) were caused by progressive and relapsing disease. With a follow up of 43 months (0-149), the median overall survival (OS) has not been reached; however, the estimated 10-year OS is 69%. Conclusion: According to our data, it seems that G-CSF-primed bone marrow is a better source of hematopoietic stem cells for allogeneic transplantation in malignant and non-malignant hematological disorders, when compared with PBSCs, due to the similar engraftment time, and a decreased incidence and severity of acute and chronic GVHD. Nevertheless, this strategy does not appear to be valid as an approach for diseases were graft versus tumor effect (GVT) is important to eradicate the malignancy, such as in CML. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 26 (5) ◽  
pp. 1021-1024
Author(s):  
Fernando Barroso Duarte ◽  
Anna Thawanny Gadelha Moura ◽  
Vaneuza Araújo Moreira Funke ◽  
Virgílio Antônio Rensi Colturato ◽  
Nelson Hamerschlak ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 873-880 ◽  
Author(s):  
Yiming Huang ◽  
Francine Rezzoug ◽  
Paula M. Chilton ◽  
H. Leighton Grimes ◽  
Daniel E. Cramer ◽  
...  

AbstractThe events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural killer (NK) cells. Durable engraftment of purified HSCs requires MHC class I K matching between HSC donor and recipient. In the absence of MHC class I K matching, HSCs exhibit impaired long-term engraftment (P = .01). Dependence on MHC class I K matching is eliminated in B6 beige mice that lack NK cell function, as well as in wild-type mice depleted of NK cells, implicating a possible regulatory role of NK cells for HSC engraftment. The coadministration of CD8+/T-cell receptor–negative (TCR-) graft facilitating cells (FCs) matched at MHC class I K to the HSC donor overcomes the requirement for MHC class I K matching between HSCs and recipient. These data demonstrate that FCs inhibit NK cell effects on the HSCs. Notably, FCs do not suppress the cytotoxic activity of activated NK cells. Enhanced green fluorescent protein–positive (EGFP+) FCs persist for one month following allogeneic transplantation, making cold target inhibition an unlikely mechanism. Therefore, MHC class I may play a critical role in the initiating events that dictate HSC engraftment and/or NK-mediated rejection following allogeneic transplantation.


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