Biomedical subjects

Pablo Rubinstein

Publications and source records attributed to Pablo Rubinstein.

9 recordsLinked to original sources

PubMed2006

Umbilical cord blood transplantation and cytomegalovirus: Posttransplantation infection and donor screening.

This study assessed the incidence of cytomegalovirus (CMV) infection after transplantation of cord blood (CB) from unrelated donors and evaluated strategies for screening CB donors. Posttransplantation CMV infection, reported in 23% of 1221 CB recipients, was associated with patient pretransplantation CMV serology (P < .001), but not with CMV serology in CB donors or their mothers. A total of 26 988 infant CB donors were evaluated by viral culture of saliva. Subgroups were evaluated by polymerase chain reaction in CB (CB-PCR) in 2 case-control studies. In the first study, 33 of 47 saliva culture-positive CB donors were confirmed by CB-PCR. All mothers of the 33 infants with confirmed CMV infection were CMV-total antibody positive, but only 1 of 3 had CMV-IgM antibody. The second study evaluated infants born to mothers with CMV-IgM antibody. Of these, 5 of 170 saliva culture-negative infants were positive by CB-PCR. The incidence of congenital CMV infection in CB donors was low (0.12%). Maternal serology had poor predictive value for CMV infection in their infant CB donors and bore no detected relationship to CMV infection in CB recipients. Saliva culture for CMV had both false-positive and -negative results. CB-PCR was a useful alternative for detecting CMV in CB donors.

Adolescent↗

PubMed2006

Why cord blood?

Cord blood, donated by mothers after the birth of their children, has become an accepted source of related and unrelated hematopoietic stem cells for marrow reconstitution. We estimate that some 7-8000 unrelated-donor cord blood transplants have been performed worldwide since 1993. The development of cord blood as a source of hematopoietic stem cells for transplantation started with the early recognition of the presence in cord blood of colony-forming cells by Knudtzon in 1974. The first cord blood transplant from a human leukocyte antigen (HLA)-identical sib to a young patient with Fanconi anemia was performed by Gluckman in 1988 and opened the way for the subsequent development of a bank for donations for unrelated patients by our group at the New York Blood Center. It is now widely recognized that two transplant-dependent variables exert strong influence on the chance for long-term recipient survival: the hematopoietic stem and progenitor cell dose and the HLA match grade. Hence, despite the generally milder graft-vs-host disease after mismatched cord blood transplantation, large and ethnically diverse inventories of cord blood are needed to permit better HLA matches and long-term survivals. In this review, a number of issues that are relevant to the history and development of an effective system for cord blood banking are discussed.

Blood Banks↗

PubMed2006

Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months.

PURPOSE: To describe outcomes after unrelated donor stem cell transplantation (HCT) in children (< 18 months at diagnosis) with acute leukemia and compare these with outcomes after human leukocyte antigen (HLA)-matched sibling donor HCT. PATIENTS AND METHODS: We compared the results of unrelated donor HCT with bone marrow (n = 85) or cord blood grafts (n = 81) and HLA-matched sibling donor HCT with bone marrow grafts (n = 101) for acute myeloid or acute lymphoblastic leukemia using Cox proportional hazards models. Unrelated donor HCT recipients were younger, more likely to have MLL gene rearrangement, to have advanced leukemia, and to receive irradiation before HCT. RESULTS: Treatment-related mortality rates were 6%, 15%, and 31% after matched sibling, unrelated donor bone marrow, and cord blood HCT, respectively. Risks of relapse, overall and leukemia-free survival were significantly associated with disease status at transplantation. Though leukemia recurrence was lowest after unrelated donor HCT in first clinical remission (CR), overall survival, and leukemia-free survival rates were similar after matched sibling and unrelated donor HCT, after adjustment for disease status. Relapse, overall and leukemia-free survival did not differ by graft type (bone marrow v cord blood) or type of leukemia. Three-year probabilities of leukemia-free survival were 49% and 54% after HLA-matched sibling and unrelated donor transplantation in first CR, respectively. Corresponding rates for those with advanced leukemia were 20% and 30%. CONCLUSION: Unrelated donor HCT should be considered for infants with acute leukemia in first CR using the same eligibility criteria as are currently used for those with HLA matched sibling donors.

Female↗

PubMed2004

Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia.

BACKGROUND: Data regarding the outcome of cord-blood transplantation in adults are scant, despite the fact that these grafts are increasingly used in adults. METHODS: We compared the outcomes of the transplantation of hematopoietic stem cells from unrelated donors in adults with leukemia who had received cord blood that was mismatched for one HLA antigen (34 patients) or two antigens (116 patients), bone marrow that had one HLA mismatch (83 patients), and HLA-matched bone marrow (367 patients). We used Cox proportional-hazards models to analyze the data. RESULTS: Cord-blood recipients were younger and more likely to have advanced leukemia than were bone marrow recipients, and they received lower doses of nucleated cells. Hematopoietic recovery was slower with transplantation of mismatched bone marrow and cord blood than with matched marrow transplantations. Acute graft-versus-host disease (GVHD) was more likely to occur after mismatched marrow transplantation, and chronic GVHD was more likely to occur after cord-blood transplantation. The rates of treatment-related mortality, treatment failure, and overall mortality were lowest among patients who received matched marrow transplants. Patients who received mismatched bone marrow transplants and those who received mismatched cord-blood transplants had similar rates of treatment-related mortality (P=0.96), treatment failure (P=0.69), and overall mortality (P=0.62). There were no differences in the rate of recurrence of leukemia among the groups. There were no differences in outcome after cord-blood transplantation between patients with one HLA mismatch and those with two HLA mismatches. CONCLUSIONS: HLA-mismatched cord blood should be considered an acceptable source of hematopoietic stem-cell grafts for adults in the absence of an HLA-matched adult donor.

Acute Disease↗

PubMed2004

Cord-blood transplants from unrelated donors in patients with Hurler's syndrome.

BACKGROUND: Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age of two years halts disease progression and prolongs life, but many children lack a bone marrow donor. We investigated the feasibility of using cord-blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler's syndrome. METHODS: Between December 1995 and October 2002, 20 consecutive children with Hurler's syndrome received busulfan, cyclophosphamide, and antithymocyte globulin before receiving cord-blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, adverse effects, and effects on disease symptoms. RESULTS: Cord-blood donors had normal alpha-L-iduronidase activity (mean number of cells, 10.53x10(7) per kilogram of body weight) and were discordant for up to three of six HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute graft-versus-host disease; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood alpha-L-iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome. CONCLUSIONS: Cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without total-body irradiation. Cord-blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease.

Blood Donors↗

PubMed2004

PTFE-covered stents improve TIPS patency in Budd-Chiari syndrome.

Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an efficient portal-systemic derivative treatment for Budd-Chiari syndrome (BCS) patients uncontrolled by medical therapy. However, the main drawback of TIPS for this condition is a very high rate of shunt dysfunction. Recently, polytetrafluoroethylene (PTFE)-covered stents have been shown to reduce the incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients treated with bare or PTFE-covered stents. The study included 25 TIPS procedures (16 bare stents and 9 covered stents) with a median follow-up period of 20.4 months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE-covered stents (P = .005). The actuarial rates of primary patency in the bare-stent group were 19% at 1 year compared with 67% in the PTFE-covered stent group (P = .02; log-rank test). The number of additional interventional procedures to maintain TIPS patency was significantly greater in the bare-stent than in the PTFE-covered stent group (1.9 +/- 1.2 vs. 0.6 +/- 0.9; P = .007). The number of patients with clinical relapses was greater in the bare-stent group compared to the PTFE-covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In conclusion, PTFE-covered stents have a considerable advantage over bare stents for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower number of reinterventions, and fewer prosthesis requirements. PTFE-covered stents are preferable in patients with Budd-Chiari Syndrome.

Actuarial Analysis↗

PubMed2003

Hematopoietic recovery after unrelated umbilical cord-blood allogeneic transplantation in adults treated with in vivo stem cell factor (R-MetHuSCF) and filgrastim administration.

Transplantation with unrelated umbilical cord blood (UCB) is marked by delayed hematologic recovery. This report summarizes two adults with chronic myelogenous leukemia (CML), who received myeloablative conditioning followed by infusion of a non-expanded single UCB graft. These CML patients were enrolled in a clinical trial incorporating concomitant in vivo administration of stem cell factor (R-MetHuSCF) and filgrastim from day of UCB infusion until attained hematopoietic recovery. Each patient engrafted fully with donor UCB, with days to absolute neutrophil count (ANC) >500/microl being 13 and 29 days, respectively. Both patients remain in cytogenetic remission at 28 months follow-up. 'In vivo UCB expansion' with administration of concomitant R-MetHuSCF and filgrastim may facilitate prompt hematologic engraftment.

Adult↗

PubMed2003

Obstetric predictors of placental/umbilical cord blood volume for transplantation.

OBJECTIVE: Umbilical cord blood is an effective alternative to bone marrow as a source of hematopoietic stem cells in transplantation. However, the amount of donor blood and the cell content that are collected may be insufficient for engraftment in some adult recipients. This study identifies obstetric factors that affect retrievable placental cord blood volume. STUDY DESIGN: A retrospective analysis of factors that were obtained by direct observation or medical record review that were related to harvested cord blood volume was conducted; the analysis involved 9205 deliveries from mothers who donated placental cord blood through the obstetric services of two New York City hospitals between 1993 and 1999. RESULTS: Obstetric factors that influenced significantly the total volume of blood that was collected were route of delivery, induction of labor, presence of a nuchal cord, infant birth weight, multiple births, placental weight, and duration of labor. The length of the umbilical cord from the venipuncture site and the length of time to cord blood collection also affected the volume that was retrieved. Maternal ethnicity was associated with cord blood yield; Caucasian mothers provided larger quantities than either African American or Asian mothers. CONCLUSION: Our results confirm that the volume of residual placental cord blood that is collected for hematopoietic stem cell transplantation is influenced by several factors, the presence of which predict the likelihood of an adequate collection. Collected volumes can be improved when a longer length of the cord is left with the placenta and when there is a shorter time between the delivery of the placenta and the collection.

Blood Volume↗

PubMed2002

Placental/umbilical cord blood for unrelated-donor bone marrow reconstitution: relevance of nucleated red blood cells.

Placental/umbilical cord blood (PCB) is a source of hematopoietic stem cells for bone marrow reconstitution. Engraftment speed and survival are related to the total nucleated cell (TNC) dose of the graft. This study explored the possible influence on engraftment of nucleated red blood cells (NRBCs) in the graft. Automated hematology analyzers were used to enumerate TNCs. NRBCs were counted by visual examination or by using an automated analyzer. Hematopoietic progenitor cells were enumerated as either colony-forming cells or CD34(+) cells. Transplant centers reported on transplant outcome in 1112 patients given PCB grafts through September 2001. NRBCs correlated with progenitor cell numbers. Both white blood cell and NRBC dose were independently predictive of myeloid engraftment speed. Because NRBC dose predicted engraftment speed, inclusion of NRBCs in the TNC count does not reduce the effectiveness of the prefreezing TNC count as an index of the quality of a PCB unit as a graft. The correlation between the number of NRBCs and the number of hematopoietic progenitor cells probably reflects the involvement of early stem cells in erythroid responses.

Bone Marrow Cells↗