Abnormal fatty acid composition in umbilical cord blood of infants at high risk of atopic disease

Abstract Conflicting results has been found on how the size of a transplant program affected the clinical outcome of hematopoietic stem cell transplant (HSCT). Some insurance carriers demand their clients to only receive HSCT in large centers, even if the service is available locally and the patients have to travel a long distance away from their home to receive the service at the approved program. Amarillo, Texas is 350 miles from Dallas and 600 miles from Houston. The HSCT program was established in Dec 2001. 18–25 transplants (autologous, allogeneic and umbilical cord blood (UCB) transplants) are performed a year. To determine whether a justification could be made to offer HSCT in a program that is small, new and community-based, we have analyzed the outcome of the adult mismatched umbilical cord blood transplants (UBCT) carried out on an unselected group of patients needing HSCT but without a matched sibling donor in our center in the last five years. Thirteen patients (8 males and 5 females) have undergone unrelated mismatched UBCT. The median age was high at 54 years (range 17 to 78). Four patients received reduced intensity conditioning regimen with Flu/Mel and 9 patients received the myelo-ablative regimen with Bu/Cy. Four patients received two units and nine single unit of umbilical cord blood. The diagnosis were: CML in CP1 (1), CML in blast crisis (2), HD relapsed within three months after autologous transplant (1), SAA (2), refractory CLL (1), ALL with multiple relapses (1), AML in CR3 (1), untreated secondary AML (2), primary refractory AML (1) and secondary AML in CR1 (1). Five patients received UCB units that were 1 antigen mismatch, 4 patients 2 antigen mismatches and 4 patients 3 antigen mismatches. GVHD prophylaxis in all cases consisted of cyclosporine A and methylprednisone. This is a group of mainly very high risk older patients. Not unexpectedly, early mortality rate was high. Death within 28 days of transplant occurred in 2 patients due to toxicity. Death within 100 days of transplant occurred in 8/13 (61.5%) patients. All the deaths occurred due to either infection or toxicity, except in one patient (age 67 years) who died due to a thrombotic stroke. Death due to disease relapse occurred in another patient 5 months after transplant for CML in blast crisis. Engraftment was documented in 9 patients. Despite the high antigen mismatches and the age of the patients, Grade I – II GVHD occurred in 7 patients and Grade III – IV in only 2 patients. With a maximum follow-up of 49 months, 4/13 (30%) patients are alive disease-free: 49+ months (age 45 years, one DRB1 mismatch), 22+ months (25 years, two antigen mismatches), 15+ months (48 years, three antigen mismatches) and 4+ months (54 years, three antigen mismatches). These results, in a group of very high risk unselected older patients in a community setting, are extremely encouraging and are comparable to those reported on younger groups of patients. Conclusions: Adult mismatched UBCT is feasible in a small program in a community setting; Patients >45 years may benefit from UBCT, even in the setting of multiple antigen mismatches; Patient selection should reduce early death and improve survival; Insurance companies should not deny patients to have transplant in their local program based on the size of the program.

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Engraftment Kinetics After Transplantation of Double Units of Umbilical Cord Blood From Unrelated Donors in Adolescents and Adults with Hematologic Malignancies.

Blood ◽

10.1182/blood.v114.22.1183.1183 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1183-1183 ◽

Cited By ~ 1

Author(s):

Miao Zhou ◽

Zimin Sun ◽

Huilan Liu ◽

Liangquan Geng ◽

Xingbing Wang ◽

...

Keyword(s):

High Risk ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Hematologic Malignancies ◽

Therapeutic Effects ◽

Promising Alternative ◽

Cell Dose ◽

The One

Abstract Abstract 1183 Poster Board I-205 Objective: To evaluate the clinical therapeutic effects and the early engraftment kinetics of the transplantation of double partially-human leukocyte antigen (HLA)-matched umbilical cord blood (UCB) units in patients with hematologic malignancies from November 2005 to March 2009. Methods: Twenty-one adults and adolescents (median age 21 years [range 10-40 years]; median weight 57 kg [range 31-76 kg]; 16 males and 5 females) with hematologic malignancies were given transplants of double UCB units. Diagnoses included 7 ALL patients, 7 AML, 5 CML, 1 Mix-AL, and 1MDS. 17 (81%) of the patients were refractory to chemotherapy and considered at high risk. All patients received myeloablative conditioning, which included Flu/Cy/TBI for 16 patients, and Bu/CY2±ATG±Ara-C for 5 patients. Graft versus host disease (GVHD) prophylaxis was CSA+MMF. The analytic method used was based on the quantitative amplification of informative polymorphic short tandem repeat (STR) regions in the recipient and donor using polymerase chain reaction (PCR), which detect engraftment and chimerism dynamically. Results: The median nucleated cell dose was 4.93×107 nucleated cell [NC]/kg range:3.26-7.70×107 NC/kg. Eighteen patients (86%) achieved hematopoietic recovery after the double UCB transplantation. The median number of days required to reach an ANC > 0.5×109/L was 20 days (14–35 days), and platelet> 20×109/L was 34.5 days (25 - 49 days). One patient's engraftment was derived from both donors, which were 6/6 HLA matched the recipient's, for six months until her death. The other 17 patients achieved sustained hematopoietic engraftment that was derived from a single dominant donor based on STR-PCR results. The median infused cell dose of the engrafted units was 2.34×107 NC /Kg (ranging from 1.87 to 4.45 ×107NC/kg), and 3.225×107CD3+/Kg (ranging from 0.51 to 13.92×107 CD3+/kg). This compared with 2.17×107 NC/Kg (range: 0.96 - 3.98×107 NC/kg) and 1.71×107CD3+/Kg (range: 0.40 - 10.65×107 CD3+/kg) in the nonsustained unit. The difference in cell doses was not significant(P=0.718 AP=0.073. By STR-PCR, the donor DNA can be detected as early as post-transplantational day 7. Seventeen patients who achieved dominant engraftment had full donor chimera (FDC) at post-transplantational day 14, and this was highly consistency with chimerisms at post-transplantational days 21 and 30. If no unit reached FDC at post-transplantational day 14, the graft would be rejected. Therefore, the result at post-transplantational day 14 could indicate the last chimerism (Kappa =1). Complications: 1) Three patients had UCB graft rejections at early period; two were adolescent ALL, one was MDS-RCMD. Depending on long-term transfusion, they all achieved long-term hematopoiesis recovery after a secondary haploidentical stem cell transplantation at post-DUCBT 33-38 day. 2) Eight/eighteen patients(44.4%)had grade±-IIacute GVHD, 2 in accessible 13 patients developed local (non-extensive) cGVHD. 3) Three patients relapsed (1 was CNSL, and 1 relapsed on cellular level and re-achieved FDC after treatment with imatinib and benzene). 4) All patients had a median follow-up of 12 months (ranging 5 months to 43 months). The one-year disease-free survival rate was 66.64%, with 6 patients died. The one hundred-day transplantation-related mortality was 14.3%; 4 died of invasive fungal infection, 1 died of body exhaustion, and 1 died of serious hepatitis. Conclusion: 1) Double-unit UCB can overcome the shortage of cell dose in one-unit UCB, and was proved to be a safe, effective, and promising alternative treatment option with good engraftment potential. 2) The total nucleated cells and CD3 cell dose were not associated with the UCB unit that would predominate. 3) The STR -PCR and capillary electrophoresis techniques can accurately evaluate grafting at an early time after UCBT. Detecting the chimerism at 14 days after UCBT can provide the information on graft implantation. 4) The relapse rate was 14.3% in 18 CB-engrafted patients with high-risk and refractory disease conditions, which suggests that UCBT has a fairly good graft versus leukemia effect. Disclosures: No relevant conflicts of interest to declare.

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Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients

Blood ◽

10.1182/blood-2011-06-361618 ◽

2011 ◽

Vol 118 (20) ◽

pp. 5689-5696 ◽

Cited By ~ 69

Author(s):

Filippo Milano ◽

Steven A. Pergam ◽

Hu Xie ◽

Wendy M. Leisenring ◽

Jonathan A. Gutman ◽

...

Keyword(s):

High Risk ◽

Confidence Interval ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Interquartile Range ◽

Historical Cohort ◽

Cord Blood Transplant ◽

Cmv Disease ◽

Cmv Reactivation

AbstractSeropositive umbilical cord blood transplant (UCBT) recipients are at increased risk for CMV complications. To reduce CMV complications, we adopted an intensive strategy that consisted of ganciclovir administered before transplantation (5 mg/kg intravenously daily from day −8 to day −2), high-dose acyclovir (2 g, 3 times daily) after transplanta-tion, and biweekly monitoring with a serum CMV PCR for preemptive therapy. Hazard rates and cumulative incidence of CMV complications along with days treated were compared in high-risk CMV-seropositive UCBT recipients who received the intensive strategy and a historical cohort who received a standard strategy. Of 72 seropositive patients, 29 (40%) received standard prophylaxis and 43 (60%) the new intensive approach. The hazard rate (HR) for CMV reactivation was lower for patients receiving the intensive strategy (HR 0.27, 95% confidence interval 0.15-0.48; P < .001) and led to fewer cases of CMV disease by 1 year (HR 0.11, 95% confidence interval 0.02-0.53; P = .006). In patients who reactivated, the intensive strategy also led to fewer days on CMV-specific antiviral therapy (median 42% [interquartile range 21-63] vs 70% [interquartile range 54-83], P < .001). Use of an intensive CMV prevention strategy in high-risk CMVseropositive UCBT recipients results in a significant decrease in CMV reactivation and disease.

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