Hematopoietic stem-cell transplantation, which is used to treat both malignant and nonmalignant conditions, was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and modulating the immune response had to be solved before the procedure could be used clinically. This review summarizes background information about hematopoietic stem-cell transplantation and discusses the current role of the procedure.

https://www.nejm.org/doi/pdf/10.1056/NEJMra052638

Hematopoietic Stem-Cell Transplantation

Background A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We evaluated this experience. Methods Placental blood was stored under liquid nitrogen and selected for specific patients on the basis of HLA type and leukocyte content. Patients were prepared for the transplantation of allogeneic hematopoietic cells in the placental blood and received prophylaxis against graft-versus-host disease (GVHD) according to routine procedures at each center. Results Outcomes at 100 days after transplantation were known for all 562 patients, and outcomes at 1 year for 94 percent of eligible recipients. The cumulative rates of engraftment among the recipients, according to actuarial analysis, were 81 percent by day 42 for neutrophils (median time to engraftment, 28 days) and 85 percent by day 180 for platelets (median, day 90). The speed of myeloid engraftment was as...

https://www.nejm.org/doi/pdf/10.1056/NEJM199811263392201

Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors

https://www2.dti.ufv.br/noticia/files/anexos/phpLlyEH4_5654.pdf

Isolation of multipotent mesenchymal stem cells from umbilical cord blood.

Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...

https://www.nejm.org/doi/pdf/10.1056/NEJM199708073370602

Outcome of cord-blood transplantation from related and unrelated donors

results Recipients of cord blood were younger than recipients of bone marrow (median, 24.5 vs. 32 years of age; P<0.001), weighed less (median, 58 vs. 68 kg; P<0.001), and had more advanced disease at the time of transplantation (52 percent vs. 33 percent, P<0.001). All marrow transplants were HLA matched, whereas 94 percent of cord-blood grafts were HLA mismatched (P<0.001). The median number of nucleated cells that were infused was 0.23¬10 8 per kilogram of the recipient’s body weight for cord blood and 2.9¬10 8 per kilogram for bone marrow (P<0.001). Multivariate analysis showed lower risks of grade II, III, or IV acute graft-versus-host disease (GVHD) after cord-blood transplantation (relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87; P=0.01), but neutrophil recovery was significantly delayed (relative risk, 0.49; 95 percent confidence interval, 0.41 to 0.58; P<0.001). The incidence of chronic GVHD, transplantation-related mortality, relapse rate, and leukemia-free survival were not significantly different in the two groups. conclusions Cord blood from an unrelated donor is an alternative source of hematopoietic stem cells for adults with acute leukemia who lack an HLA-matched bone marrow donor.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa041469

Transplants of Umbilical-Cord Blood or Bone Marrow from Unrelated Donors in Adults with Acute Leukemia

The clinical manifestations of Fanconi’s anemia, an autosomal recessive disorder, include progressive pancytopenia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi’s anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi’s anemia who received cryo-preserved umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifically for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]).

Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an hla-identical sibling

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.

Oncolytic poliovirus for human tumors

i .lini tumors of all grades and histolA3gica! types from 72 adults and 48 children were analyzed for mutations of the TP53 gene, loss of heterozygosity (LOH) for I7p, and accumulation of TP53 protein to determine whether the incidence and type of TP53 alterations differ among tumors of different histolA3gica! type and between tumors from adults and chil dren. These tumors were also evaluated for LOH for chromosome 10 and for amplification of the epidermal growth factor receptor, C-MYC, NMYC, GLI, platelet-derived growth factor receptor-a, and murine double minute 2 genes to determine the patterns of molecular alterations involved in the progression of these neoplasms. Seventeen of the 120 tumors con tained mutations of the TP5.AŒgene. One of the tumors with TP5.1 gene mutation was from one of the 48 patients less than 18 years of age. Twelve of the 17 tumors with mutations occurred among the 27 patients in the 18â€”15-yearage group, while 4 tumors with mutations were among the 45 patients more than 45 years old. There was also an increased incidence of TP53 mutation in patients with anaplastic astrocytoma histology. How ever, no significant association between presence of TP53 mutation and patient survival was observed. These studies demonstrate that TP53 gene mutations are a common mechanism for glial cell neoplasms in the 1845-year age group but are unrelated to progression and advanced histo lA3gica! grade. LOH for chromosome 10 and gene amplification, however, occurring in 82 and 40%, respectively, of glioblastoma multiforme, whether seen alone or along with TP53 gene alterations, are related to advanced histolA3gica! grade of the tumor. In childhood gliomas, in con trast, TP53 gene alterations, LOH for 17p and lOq, and gene amplification are uncommon in tumors of all grades, suggesting that presently unknown mechanisms are responsible for the genesis and progression of these tumors.

Alterations of the TP53 Gene in Human (Â¿liornas1

Chapter 25 – Ependymoma

Purpose: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). Patients and Methods: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) melphalan (MEL) or busulfan (Bu) MEL regimens and ASCR. Results: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX MEL, and one patient received BU MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. Conclusion: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma. J Clin Oncol 21:2187-2191. © 2003 by American Society of Clinical Oncology.

Henry S. Friedman

Papers

Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an hla-identical sibling

Oncolytic poliovirus for human tumors

Alterations of the TP53 Gene in Human (Â¿liornas1

Chapter 25 – Ependymoma

High-Dose C hemotherapy W ith A utologous S tem-Cell R escue in C hildren a nd A dults W ith N ewly D iagnosed P ineoblastomas