Fluorescence in situ hybridization FISH and cytogenetics for chromosomal abnormalities associated with primary malignancy or emerging myelodysplastic syndrome MDS. Polymerase chain reaction PCR based tests for molecular abnormalities associated with primary malignancy. Chimerism studies percentage of donor and recipient cells, sort cells for T lymphocytes and granulocytes Chimerism studies from peripheral blood in sorted T cells and granulocytes.
Microbiologic studies if suggested ; granulomatous disease mycobacterium or viruses HHV-6 can lead to GF.
Abdominal computed tomography CT scan or ultrasound to rule out splenomegaly and associated hypersplenism. Granulocyte-colony stimulating factor G-CSF or erythropoietin, but if no response after some time, these may be discontinued. Aggressive diagnostic measures for early detection of GF: Closely follow chimerism studies, particularly in T-cells.
Decrease immunosuppression when secondary GF or decline in chimerism is detected. This may increase risks of severity of GVHD. Infusion of a booster dose of donor hematopoietic stem cells to support hematopoietic engraftment.
This is feasible if no active GVHD is present. The prolonged pancytopenia can be fatal. A second allogeneic transplantation may be needed. In some cases conditioning with reduced doses of cytotoxic agents or further immunosuppression with ATG, corticosteroids, plus cyclosporine is given before the second infusion. For second graft infusions, these reduced intensity conditioning RIC regimens are associated with less toxicity and better survival than myeloablative regimens.
Humans are quite adaptable. This change, although more accurate, hardly sheds light on this complex issue but at least we eliminate the ambiguity of primary and secondary, a minor victory.
They also use the term graft function rather than graft-failure, but this difference seems less important. The authors previously reported abnormalities of bone marrow endosteal cells, perivascular cells and endothelial cells in persons with late poor graft function. The question is whether these data are credible and whether they help us understand graft-failure after haematopoietic cell transplants.
The studies are carefully conducted and the investigators reliable. Surely some of the abnormalities they describe are associated with occasional cases of early and late poor graft function. However, it seems rather unlikely that there would be a single aetiology of poor graft function in such a diverse clinical setting. It is also a bit curious as to why some of the subjects with late graft-failure could have seemingly normal bone marrow function for prolonged intervals if they had a fundamental abnormality of the bone marrow microenvironment unless this is an acquired defect.
However, associations are not cause and effect and we are always left with the question whether these abnormalities cause or result from defective bone marrow function. En guarde for the logical fallacy of post hoc ergo propter hoc. Regardless of how convinced you are by these data, the study is interesting and deserves critical discussion.
Do not bet the farm on a successful outcome in such a heterogeneous clinical setting. As the authors indicate, several other risk factors for poor graft function are reported.
Back to the Kong et al. It seems rather unlikely that the impact of all of these confounded variables on bone marrow function would end up in a common histological pattern of bone marrow failure in a cohort of 10 subjects. Their finding may be an example of making a complex issue too simple unless we envision the abnormalities they describe as the effect rather than the cause of early bone marrow failure.
Hardly a public health problem, although the incidence of early graft-failure in recipients of HLA-haplotype-matched transplant such as those studied by Kong et al.
A few suggestions follow: first, I suggest that we adopt the terms early and late rather than primary and secondary when the bone marrow heads south. This change sheds no new light on this issue, but at least we have accurate temporal descriptors. Second, I suggest that we adopt the term graft-failure rather than poor graft function as we do not know how well the haematopoietic cells are functioning versus quantitative abnormalities in normally functioning cells.
Our readout of graft-failure is, of course, arbitrary and might reasonably be numbers of short-lived cells such as granulocytes and platelets in the blood. The reader may wonder why, with so many caveats to the Kong et al. Interleukinactivated natural killer cells can support hematopoiesis in vitro and promote marrow engraftment in vivo. Blood 80 3 —7. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.
Science — Antibody-mediated marrow failure after allogeneic bone marrow transplantation. Blood 74 5 — Preformed antibody, not primed T cells, is the initial and major barrier to bone marrow engraftment in allosensitized recipients. Blood 3 — The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure.
Blood 13 —8. Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood 25 —7.
Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood 22 — Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT.
Bone Marrow Transplant 47 4 — High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem cell transplantation. Transplantation 88 8 Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplant 50 9 — Transplantation 86 5 — Blood 23 — Nat Med 14 1 — Therapeutic efficacy of polyclonal tregs does not require rapamycin in a low-dose irradiation bone marrow transplantation model. Transplantation 92 3 —8.
Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment. Blood 18 — In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature —9.
Exp Hematol 34 1 — Shatry A, Levy RB. In situ activation and expansion of host tregs: a new approach to enhance donor chimerism and stable engraftment in major histocompatibility complex-matched allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 15 7 — PLoS One 11 1 :e J Immunol 12 —9. Zhao K, Liu Q. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. J Hematol Oncol 9 1 :1—9. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells.
Leukemia 21 8 —8. Cotransplantation of ex vivo—expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation.
Blood 7 —7. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 11 5 — Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I-II clinical trial.
Bone Marrow Transplant 43 6 — Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion-induced bone marrow failure. A mouse model of lymphocyte infusion-induced bone marrow failure. Exp Hematol 32 12 — Allogeneic Th1 cells home to host bone marrow and spleen and mediate IFNgamma-dependent aplasia. Biol Blood Marrow Transplant 19 6 — Increased type 1 immune response in the bone marrow immune microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant 22 8 — Biol Blood Marrow Transplant 6 6 — Goals of a bone marrow transplant depend on your individual situation, but usually include controlling or curing your disease, extending your life, and improving your quality of life. Some people complete bone marrow transplantation with few side effects and complications. Others experience numerous challenging problems, both short and long term. The severity of side effects and the success of the transplant vary from person to person and sometimes can be difficult to predict before the transplant.
It can be discouraging if significant challenges arise during the transplant process. However, it is sometimes helpful to remember that there are many survivors who also experienced some very difficult days during the transplant process but ultimately had successful transplants and have returned to normal activities with a good quality of life.
Explore Mayo Clinic studies of tests and procedures to help prevent, detect, treat or manage conditions. Living with a bone marrow transplant or waiting for a bone marrow transplant can be difficult, and it's normal to have fears and concerns. Having support from your friends and family can be helpful. Also, you and your family may benefit from joining a support group of people who understand what you're going through and who can provide support.
Support groups offer a place for you and your family to share fears, concerns, difficulties and successes with people who have had similar experiences. You may meet people who have already had a transplant or who are waiting for a transplant.
Bone marrow transplant care at Mayo Clinic. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Overview A bone marrow transplant is a procedure that infuses healthy blood-forming stem cells into your body to replace your damaged or diseased bone marrow.
Allogeneic stem cell transplant Autologous stem cell transplant. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references AskMayoExpert.
Hematopoietic stem cell transplant. Mayo Clinic; Hoffman R, et al. Overview of hematopoietic stem cell transplantation. In: Hematology: Basic Principles and Practice. Philadelphia, Pa. Accessed July 8, Blood-forming stem cell transplants. National Cancer Institute. Majhail NS, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation. Diseases treatable by transplants. National Marrow Donor Program.
Accessed Aug. Graft-versus-host disease. Rochester, Minn. Blood and marrow stem cell transplantation. Autologous stem cell transplant. Blood and bone marrow transplant.
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