scholarly journals Last Marrow Standing: Bone Marrow Transplantation for Acquired Bone Marrow Failure Conditions

2012 ◽  
Vol 7 (4) ◽  
pp. 292-299 ◽  
Author(s):  
Aaron T. Gerds ◽  
Bart L. Scott
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Failure Conditions

scholarly journals Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1043-1046
Author(s):  
GD Goss ◽  
MA Wittwer ◽  
WR Bezwoda ◽  
J Herman ◽  
A Rabson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Cell Activity ◽  
High Dose

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.

Age-Adjusted Telomere Length Is Not Associated with Variation in Hematological Parameters in Ageing Women

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3102-3102
Author(s):  
Isabelle Fleury ◽  
Sylvie Provost ◽  
Claude Belisle ◽  
Lambert Busque
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Telomere Length ◽  
Marrow Transplantation ◽  
Copy Number ◽  
Bone Marrow Failure ◽  
Telomere Maintenance ◽  
Hematological Parameter ◽  
Allogeneic Bone ◽  
Potential Biomarker

Abstract Background. Telomeres play a crucial role in maintaining physical integrity of chromosomes. In the absence of telomerase, telomere length (TL) shortens with each cell division up to a critical threshold where cellular senescence occurs. TL is inversely correlated with age, is longer in women than in men, and demonstrates a strong heritability. Normal blood counts are maintained through out life by an extraordinary number of cell divisions rendering telomere maintenance primordial to prevent stem cell exhaustion. In fact, some cases of bone marrow failure syndromes, such as aplastic anemia and dyskeratosis congenital, have been linked to mutation in the telomerase gene; and stressed hematopoiesis, such at it occurs during the first year following allogeneic bone marrow transplantation induces TL shortening. We hypothesized that individuals with shorter TL may have lower blood counts and a decreased bone marrow reserve. The evaluation of TL as a potential biomarker of ageing hematopoiesis is important in the context of bone marrow transplantation performed with increasingly old donors. Methods. We measured TL in 1583 women, predominantly aged over 60, all originating from 288 French-Canadian families using a real-time quantitative PCR method that measures the number of telomere repeats relatively to the copy number of a single copy number gene. Telomeres were adjusted for age. Pearson or Spearman correlations were used to determine association between age-adjusted TL (aTL) and hematological parameter according to, respectively, whether or not a normal distribution was observed for these data. A Bonferroni correction was further applied to set the statistical significance threshold. Results. aTL varied significantly between individuals of the cohort, but no correlation was detected with hemoglobin levels (−0,001; p=0,978), mean corpuscular volume (−0,031; p=0,403); leucocytes (0,055; p=0,139); neutrophils (0,078; p=0,036), monocytes, (0,059; p=0,113), eosinophils (−0,032; p=0,394) and platelets (0,030; p=0,428) counts. Conclusion. Based on our analysis, TL do not predict blood cells counts in ageing women and may not be a useful biomarker for donor selection. This could also suggest that there is a threshold beyond which TL has an effect on hematopoiesis and that point was not reached in our cohort.

Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3624-3624
Author(s):  
Nicholas Economou Khan ◽  
Philip S. Rosenberg ◽  
Blanche P. Alter
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Standard Care ◽  
Bone Marrow Failure ◽  
Event Free Survival ◽  
Free Survival ◽  
Increased Risk ◽  
The Mean

Abstract Background: Fanconi anemia (FA) is a primarily autosomal recessive bone marrow failure and cancer predisposition syndrome associated with mutations in the FA/BRCA DNA damage response pathway. The median age at diagnosis of FA is 7 years; the diagnosis is often made due to recognition of characteristic birth defects. Over half of patients with FA develop severe bone marrow failure (BMF) by age 50 years, one in ten develop acute myeloid leukemia (AML), and one in four develop a solid tumor (ST) as their first event. Successful allogeneic bone marrow transplantation (BMT) is potentially curative of FA's hematologic manifestations but introduces risks of transplant-related mortality (TRM) and morbidity. We hypothesized that preemptive bone marrow transplantation (PE-BMT) for individuals diagnosed prior to the development of BMF, AML, or ST, would increase event-free survival (EFS) if the risks associated with transplantation were sufficiently low. Methods: We developed a mathematical decision model (Markov) of EFS with the assumption that successful PE-BMT would eliminate the risks of BMF and AML, but would introduce a procedural risk of TRM. We modeled the EFS of PE-BMT at variable ages at decision ranging from birth to 30 years, and without and with an increase in the rate of ST following BMT above the level in untransplanted patients with FA. We developed our model using empirical estimates of the age-specific conditional probabilities of BMF, AML, and ST (Alter et al, BJH, 2010), and a 4.4-fold estimated increased risk of ST following BMT (Rosenberg et al, Blood, 2005). We tested the sensitivity of the model over a range of values for TRM and an increased risk of ST following BMT, and evaluated the model using TreeAge Pro 2014 (TreeAge Software, Inc, Williamstown MA, http://www.treeage.com). Results: Children diagnosed at age 7 years receiving standard care could expect to live an additional 16 years before experiencing BMF, ST, or AML, and thus survive free of an event until an average age of 23 years. If those children instead received PE-BMT with a 10% risk of TRM, they could expect to survive an additional 29 years and be cancer-free until an average age of 36 years. However, if PE-BMT were to increase the rate of ST 4.4-fold, PE-BMT would only increase the mean EFS by 2 years over standard care, until an average age of 25 years. PE-BMT would increase the mean EFS at all ages if TRM was ≤10% and the risk of ST was the same as in untransplanted patients. PE-BMT would decrease the mean EFS when performed after age 9 years if there was 10% TRM and a 4.4-fold increased rate of ST. PE-BMT at age 18 years with 10% TRM would increase the mean EFS if it did not affect the trajectory to ST, but would decrease the mean EFS if it modestly increased the rate of ST (≥2.2-fold). Conclusions: PE-BMT in patients with FA may provide an event-free survival benefit so long as the risk of TRM appears to be low (≤10%) and the regimen has little or no impact on the development of ST. The decision was particularly sensitive to the increase in ST following BMT. Our model suggests that older ages at decision, higher risks of TRM, and greater relative risks of ST following transplant would lead to PE-BMT being a less desirable strategy. Our estimates of event-free survival may be used to inform shared decision making between providers and families, with attention paid to patient values and the morbidity associated with BMT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

2007 ◽  
Vol 2 (1) ◽  
Author(s):  
Bernd Gruhn ◽  
Joerg Seidel ◽  
Felix Zintl ◽  
Raymonda Varon ◽  
Holger Tönnies ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Dna Ligase ◽  
Dna Ligase Iv ◽  
Ligase Iv

scholarly journals Bone marrow transplantation for Fanconi anemia

Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2856-2862 ◽  
Author(s):  
E Gluckman ◽  
AD Auerbach ◽  
MM Horowitz ◽  
KA Sobocinski ◽  
RC Ash ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Unrelated Donor ◽  
Bone Marrow Transplants ◽  
Transplant Outcome ◽  
Factors Associated ◽  
Increased Risk

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

scholarly journals Successful reduced-intensity bone marrow transplantation in a patient with bone marrow failure associated with Seckel syndrome

2008 ◽  
Vol 142 (4) ◽  
pp. 675-676 ◽  
Author(s):  
Melissa Rayburg ◽  
Stella M. Davies ◽  
Parinda A. Mehta ◽  
Michelle Crockett ◽  
Sonata Jodele
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Bone Marrow Failure ◽  
Seckel Syndrome ◽  
Reduced Intensity

scholarly journals How I treat paroxysmal nocturnal hemoglobinuria

Blood ◽  
2009 ◽  
Vol 113 (26) ◽  
pp. 6522-6527 ◽  
Author(s):  
Robert A. Brodsky
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Allogeneic Bone Marrow Transplantation ◽  
Clinical Manifestations ◽  
Allogeneic Bone ◽  
Curative Therapy ◽  
Blood Disorder

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal blood disorder that manifests with hemolytic anemia, bone marrow failure, and thrombosis. Many of the clinical manifestations of the disease result from complement-mediated intravascular hemolysis. Allogeneic bone marrow transplantation is the only curative therapy for PNH. Eculizumab, a monoclonal antibody that blocks terminal complement activation, is highly effective in reducing hemolysis, improving quality of life, and reducing the risk for thrombosis in PNH patients. Insights into the relevance of detecting PNH cells in PNH and other bone marrow failure disorders are highlighted, and indications for treating PNH patients with bone marrow transplantation and eculizumab are explored.

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