Birth Order and Outcome in HLA-Identical Sibling Donor Hematopoietic Stem Cell Transplants. Impact of a Sequential Fetomaternal - Maternofetal Cell Transfer?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2034-2034
Author(s):  
Christoph M. Bucher ◽  
Dominik Heim ◽  
Andreas Buser ◽  
Jakob R. Passweg ◽  
Alois Gratwohl
Keyword(s):  
Stem Cell ◽  
Birth Order ◽  
Myeloid Leukemia ◽  
Cell Transfer ◽  
Black Line ◽  
Cell Transplants ◽  
Group A ◽  
Grade Ii ◽  
Stem Cell Transplants ◽  
Group B

Abstract Fetomaternal and maternofetal cell transfer have been described. Their clinical relevance is unknown. We hypothesized that firstborn siblings could tolerize their siblings born thereafter through sequential fetomaternal-maternofetal cell transfer. Hence, stem cell transplants within a family from a firstborn sibling (group A) should result more graft-versus-host disease (GvHD) and worse overall survival than transplants to a firstborn donor (group B). Results of a retrospective single center cohort analysis of 321 HLA-identical sibling donor hemopoietic stem cell transplants showed a survival of 48.3% (+/−10.9%) at 10 years in the group with firstborn donors (group A, 110 patients) as compared to 63.2 (+/−10.6%) in the group with firstborn recipients (group B, 105 patients; p<0.02) and a RR of death after adjustment for other risk factors of 2.6 (CI 1.45–4.66; p<0.001) for the group with firstborn donors. These results support the concept of a clinically relevant tolerizing effect of birth order, possibly mediated by fetomaternal cell transfer in man. Patients characteristics and outcomes Birth Order Donor First Sibling Recipient First Sibling n 110 105 Donor Age median (range) 30.1 (4.9–68) 25.4 (0.4–59.1) p=0.005 Recipient Age median (range) 25.4(3.2–62.1) 30.8 (2.2–63.0) Number of Siblings 2 67 69 n.s. 3 26 22 >3 17 14 Diagnosis n.s. Acute myeloid leukemia n 33 26 Acute lymphoblastic leukemia n 24 24 Chronic myeloid leukemia n 23 23 Lymphoproliferative disorders n 14 13 Severe aplastic anemia n 11 12 Myelodysplastic syndromes n 5 7 Stem Cell Source n.s. Bone Marrow n 71 73 PBSCT n 39 32 Conditioning n.s. With totoal body irradiation n 18 22 Without total body irradiation n 92 83 Outcomes Survival at 10 yrs % 48.3 63.2 p<0.02 Relapse at 3 yrs. % 26 20 n.s. Acute GvHD p=0.017 < Grade II n 46 61 >= Grade II n 64 44 Chronic GvHD n.s. none n 28 30 n.a. n 29 17 Limited n 32 30 Extensive n 21 23 Figure 1: Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient. Figure 1:. Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.

Bacterial, Viral and Fungal Infections in Patients after Allogeneic Stem Cell or Bone Marrow Transplantation - A Comparison between Patients with Related and Patients with HLA-Matched Non-Related Stem Cell Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4978-4978
Author(s):  
Christina T. Rieger ◽  
Johanna Tischer ◽  
Helmut Ostermann
Keyword(s):  
Bone Marrow ◽  
Candida Albicans ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Stem Cell Source ◽  
Cell Source ◽  
Group A ◽  
Group B

Abstract Bacterial, viral and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic stem cell transplantation (SCT). We investigated whether patients with related stem cell donors (group A) developed infections less frequently than patients with HLA-matched, non-related donors (group B). Fifty-nine consecutive patients treated at our transplantation unit between April 2004 and January 2005 were included into the analysis. We documented demographic and clinical characteristics at baseline, treatment, clinical course, microbiological examinations, clinical and radiological signs of infection and mortality. Of the total 59 patients analyzed, 22 received stem cells from related and 37 from HLA-matched non-related donors. Both groups were well balanced regarding age and weight. 50% of the patients in group A and 60% in group B were male. Most frequent diagnoses were acute myeloid leukemia (30 of 59 patients [50.8%]; group A: 68.2%; group B: 40.5%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%) and chronic myeloid leukemia (10.2%). Bone marrow was more often the stem cell source in group A (45.5%/ 10 patients) than in group B (10.8%/ 4 patients), peripheral stem cell transplantation respectively was predominant in the unrelated group (86.5%/ 32 patients) versus the family donor group (54.5%/ 12 patients), cord blood was used as unrelated stem cell source in1 patient (2.7%). Clinically documented infections occurred in 6% in group A and in 14% in group B. Pulmonary infiltrates were observed more frequently in group A (11 patients/ 50%) than in group B (16 patients/ 43.2%). The predominant findings were atypical infiltrates (total 16 patients), followed by signs of fungal (total 7 patients) and bacterial pulmonary infiltration (total 4 patients). Microbiologically documented infections were detected in all patients. The average number of pathogens was equal in both groups. Detected pathogens were HHV-6 (48 patients), coagulase-negative Staphylocci (17 patients), EBV (14 patients) and CMV (11 patients). Three fungal infections were detected by microbiological approaches in group A (2 × Candida albicans, 1 × Pitysporum ovale) compared to nine fungal infections in group B (5 × Candida albicans, 1 × Candida glabrata, 1 × Candida parapsilosis, 2 × Geotrichum capitatum). Two years after transplantation, 55.9% of patients were alive (group A: 68.2%; group B: 48.6%). Patients with AML had a two-year survival of 50% (group A: 53.3%; group B: 46.7%). In our study, we observed no clear relation between frequency of infection and donor type, yet there was a trend towards more invasive fungal infections in the unrelated group (13% group A vs. 24% group B).

A modified EBMT risk score predicts the outcome of patients with acute myeloid leukemia receiving allogeneic stem cell transplants

2011 ◽  
Vol 86 (4) ◽  
pp. 305-316 ◽  
Author(s):  
Philipp G. Hemmati ◽  
Theis H. Terwey ◽  
Philipp le Coutre ◽  
Lam G. Vuong ◽  
Gero Massenkeil ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Cell Transplants ◽  
Stem Cell Transplants ◽  
Acute Myeloid

scholarly journals A Preclinical Non-Human Primate Model to Test Reversible Myeloablation Following IV Busulfan Therapy without Stem Cell Rescue

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1868-1868
Author(s):  
Nadim Mahmud ◽  
Amit Khanal ◽  
Simona Taioli ◽  
Emre Koca ◽  
Sujata Gaitonde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Platelet Counts ◽  
Stem Cell Rescue ◽  
Cd34 Cells ◽  
Group A ◽  
Pre Treatment ◽  
Wbc Count ◽  
Group B ◽  
Acute Myeloid

Abstract Busulfan is a standard drug utilized in stem cell transplantation for myeloid malignancies, however it is not used in any induction or salvage chemotherapy regimen in these diseases. Non-human primates (NHP) represent a useful model for preclinical evaluation of chemotherapy-related toxicity. In order to identify what dose of IV busulfan could be tested in clinical studies for acute myeloid leukemia, we utilized NHP to determine the highest dose of IV busulfan needed to achieve reversible myelosuppression in unperturbed bone marrow (BM). Nine adult baboons (Papio anubis) were divided into three groups (n=3/group) for this study. Group A received the lowest dose of busulfan 6.4 mg/kg (1.6 mg/kg/day x 4 days), Group B received 8 mg/kg (3.2 mg/kg on day 1 and 1.6 mg/kg on day 2-4) and Group C received 9.6 mg/kg (3.2 mg/kg/day day 1-2 and 1.6 mg/kg/day day 3-4). Peripheral blood (PB) complete blood count (CBC), and BM CD34+ cells, colony forming unit (CFU) were monitored over 90 days after busulfan. Maximum suppression of WBC count, hemoglobin (Hb) and platelet counts in the PB of baboons in all 3 groups were observed around day 15. The suppression of WBC was 57 ± 4%, 58 ± 4% and 53 ±10% in group A, B and C respectively (group A: p = 0.006, group B: p = 0.03, group C: p = 0.07). The suppression of absolute neutrophil counts (ANC) in group A, B and C were 85 ± 2%, 8 4± 1% and 82± 5% respectively. Similarly the minimum post-busulfan Hb levels were 10± 0.6 g/dl, 10± 1g/dl, 10± 0.6g/dl in group A, B and C respectively. The suppression of platelet counts were 84 ± 6%, 81 ± 7% and 81 ± 9% in group A, B and C respectively. Taken together, PB CBC results indicate that at day 15, despite administering a higher dose of busulfan the maximum depletion of ANC, Hb and platelet was comparable among the three groups. At day 90, the PB WBC, Hb and platelet counts returned within normal ranges. Notably, in the group receiving the highest dose of busulfan (Group C) the PB WBC counts at day 90 displayed 76 ± 9% recovery and platelets a 79 ± 13% recovery. Extra-hematopoietic toxicity, including weight loss, was not significant in any group of animals. Then we examined CD34+ cells and CFU content of BM prior to and following busulfan therapy. Baboons receiving the lowest dose of busulfan (Group A) displayed 75 ± 19% CD34+ cell suppression, while the intermediate group B had 90 ± 9%, and the group C which received the highest dose of busulfan had 98 ± 0.6 % suppression. The CD34+ cell recovery at day 90 was 56%, 35% and 24% in group A, B and C, respectively, suggesting that the BM CD34+ cell compartment requires more time to recover despite near normal CBC numbers. Similarly, at day 15 the suppression of BM CFU in group A, B and C was 71 ± 10% , 86 ± 8% and 91 ± 5% respectively. Although the suppression in PB WBC count was not distinct the absolute number of CD34+ cells and CFU content of BM varied based on busulfan dose administered. At day 90 the recovery of BM CFU in group A, B & C were 51 ± 15% , 79 ± 15% and 53 ± 9%, respectively. Although there was no significant intergroup difference in degree of CFU plating efficiency, pre-busulfan versus day 90 CFU recovery in group C was statistically significant (p = 0.02) . These results further validate the hierarchy of CD34+ cells and CFU in contrast to more mature PB cells and the cell populations targeted by busulfan, emphasizing regulatory systems governing homeostasis are likely maintained by reserved BM precursors and progenitor cells. Despite near normalization of blood counts, the relatively primitive BM CD34+ cells and CFU content require longer time to return to pre treatment levels. BM biopsy results indicate a return of cellularity and tri-lineage hematopoiesis comparable to pre-treatment levels in all three groups by day 90. Taken together, our study showed that when busulfan is administered in a dose range of 6.4 to 9.6 mg/kg in an NHP model, it is capable of inducing reversible myeloablation with tolerable toxicity without requiring stem cell rescue or blood transfusions. Our results also indicate that about 30 to 40% BM reserve is capable of maintaining normal PB cell counts. Based on the results, we plan to design a phase 1/2 clinical trial where non-myeloablative doses of IV busulfan will be tested as salvage therapy in patients with acute myeloid leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Positive selection for CD90 as a purging option in acute myeloid leukemia stem cell transplants

2007 ◽  
Vol 74B (1) ◽  
pp. 9-16 ◽  
Author(s):  
Nicole Feller ◽  
Angèle Kelder ◽  
Guus Westra ◽  
Gert J. Ossenkoppele ◽  
Gerrit J. Schuurhuis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Positive Selection ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cell ◽  
Cell Transplants ◽  
Selection For ◽  
Stem Cell Transplants ◽  
Acute Myeloid
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