- Email: [email protected]
Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank
Blood Cells, Molecules and Diseases 57 (2016) 71–73
Contents lists available at ScienceDirect
Blood Cells, Molecules and Diseases journal homepage: www.elsevier.com/locate/bcmd
Short Communication
Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank Maria Screnci a,⁎, Emilia Murgi a, Veronica Valle a, Anna Tamburini b, Maria Grazia Pellegrini c, Sabrina Strano d, Francesca Corona a, Eleonora Barbacci Ambrogi a, Gabriella Girelli a a
Immunohaematology and Transfusion Medicine Unit, Azienda Policlinico Umberto I, Via Chieti N 7, 00161 Rome, Italy Immunohaematology and Transfusion Medicine Unit, Ospedale S. Eugenio, P.le dell'Umanesimo n10, 00144 Rome, Italy Obstetrics and Gynecology Unit, Ospedale S Giovanni Calibita, Piazza Fatebenefratelli n2, 00186 Rome, Italy d Obstetrics and Gynecology Unit, Ospedale S Pertini, Via dei Monti Tiburtini n 385, 00157 Rome, Italy b c
a r t i c l e
i n f o
Article history: Submitted 24 November 2015 Revised 22 December 2015 Accepted 29 December 2015 Available online 3 January 2016 Editor: Mohandas Narla Keywords: Alternative donor Related cord blood banking Family-directed cord blood banking Umbilical cord blood transplantation Stem cell transplantation
a b s t r a c t Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a “Sibling cord blood donor program for hematopoietic cell transplantation”. Here we report results of this project started 20 years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Hematopoietic cell transplantation (HCT) is the main curative treatment in patients with malignant and non malignant hematological disorders or genetic diseases, such as immunodeficiencies, inherited metabolic diseases and other conditions, who may benefit from a human leucocyte antigen (HLA) matched sibling donor. As umbilical cord blood (UCB) is a graft source [1] and UCB transplantation from HLA-identical sibling provides good results in children [2–5], then family directed UCB collection and banking is recommended in presence of medical indication for related UCB transplantation in a donor's sibling, particularly for patients in urgent need for transplantation who cannot wait for the donor's sibling bone marrow to be collected [6–8]. With the aim to provide access to all patients in need, in 1994 we started a “Sibling cord blood donor program for HCT”. All families entered into the study were experiencing a pregnancy and already caring for, or at high risk to have, a child with disease treatable by allogeneic HCT. Six
⁎ Corresponding author. E-mail addresses: [email protected], [email protected] (M. Screnci), [email protected] (A. Tamburini), [email protected] (M.G. Pellegrini), [email protected] (S. Strano).
http://dx.doi.org/10.1016/j.bcmd.2015.12.010 1079-9796/© 2016 Elsevier Inc. All rights reserved.
hospitals collaborated to this program. Herein we report our twenty year single center experience. 2. Patients and methods Data were obtained over a 20 years period between 1994 and 2014. As December 2014, a total of 194 families were enrolled for related UCB harvesting and cryostorage. Nine families were recruited more than once and potentially candidate to 19 UCB collections: in these cases, the patients were considered only once, at first collection's date. Patients' characteristics are detailed in Table 1. Seven families were recruited because of at high risk to have a child with disease treatable by HCT: both parents β thalassemia trait carriers and healthy or β thalassemia trait carrier newborn. The UCB procurements were mostly required by referring clinicians for patients with hematological malignancies (69%). Among malignancies, acute lymphoblastic leukemia was the most common diagnosis, while thalassemia major was the most frequent disease among non malignant conditions. Since according to applicable governmental rules family-directed UCB collection and storage are under the responsibility of public CB banks, then all families were addressed to UCB collection sites already collaborating in unrelated UCB donation and banking. Therefore,
72
M. Screnci et al. / Blood Cells, Molecules and Diseases 57 (2016) 71–73
Table 1 Patients' Characteristics. Characteristics Age (yy) Body weight (kg) at UCB collection Gender (male/female) Diagnosis: Malignant hematological diseases Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Myelodysplastic syndrome Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Chronic Myeloid Leukemia Non malignant hematological diseases Thalassemia major Blackfan–Diamond anemia Aplastic anemia Sickle cell disease Fanconi anemia Other Solid tumors Immunodeficiency diseases Metabolic diseases Other conditions Total
N
Median
(Range)
5.5 21
(1–17) (6–72)
112/75 129 91 13 10 9 2 4 38 14 8 5 5 1 5 9 5 1 5 187
standardized UCB collection, labeling, storage and shipment operating procedures were well known to all the involved personnel of the collection facilities. No family was charged for UCB collection or banking. With reference to local rules, written informed consent was obtained from the donor mother before delivery, as well as consent for confidential information, mandatory infectious testing, tissue typing and storage of units. Testing for infectious disease was performed on mother's serum and the screening included hepatitis B virus (HBV) surface antigen, antibodies to hepatitis C virus (HCV), HIV 1–2, and syphilis. Afterwards, since 2004 nucleic acid testing (NAT) was added to screen HCV, HIV and HBV. To prevent cell loss, all UCB collections were cryopreserved without volume reduction manipulation: cryoprotectant solution was prepared from dimethyl sulfoxide (DMSO) and human albumin to reach a final DMSO concentration of 10%. UCB units were frozen by controlled rate freezer and then transferred into liquid nitrogen based storage tanks, maintained at less than −150 °C and continuously monitored. To screen the collected UCB for transplantation suitability, cell and progenitor content evaluation, microbiological testing, red blood cells phenotype and HLA typing were carried out. HLA matching between patient and UCB donor was based on serological or molecular class I HLA typing and high resolution molecular class II typing. A descriptive analysis was made: the data are presented as absolute values, percentages, median values and range.
macrophage (CFU-GM) content were 2.3 × 106 (range 0.03– 17.2 × 106) and 4.76 × 105 (range 0.3–37.9 × 105) respectively. As detailed in Table 2, to date, HLA typing has been performed for 152 UCB collections while for 52 is pending: since 64 potential recipients have not been typed yet, HLA compatibility degree is evaluable only for 88 donor/recipient pairs and as expected about a third of UCBs resulted HLA identical to the intended recipient. Since the beginning of the program, the UCB collections have reached a median storage time of 7.8 years (range 0.1–20.3 years) and a total of 15 units has been transplanted. Considering HLA-identical donor/recipient pairs, a total of 15 patients (55.5%) were grafted with the intended fully matched UCB unit; most patients (53%) received UCB in conjunction with a small volume of bone marrow from the same HLA-identical sibling donor. Table 3 gives an overview of the transplanted patients. UCB units have been grafted after a median time of storage of 12 months (range 3–49 months). Biological characteristics of transplanted UCB units are summarized as follows: the median TNC count was 88.2 × 107 ranging from 38.3 to 203.3 × 107, the median CD34 + cell count and CFU-GM content were 2.0 × 106 (range 0.6– 9.4 × 106) and 3.5 × 105 (range 0.9–14.5 × 105) respectively. All evaluable patients engrafted, a patient with acute myeloid leukemia died 10 days after transplantation. For patients who engrafted, the median time to neutrophil recovery after transplant was 22.5 days (range, 17 to 45). The median time to platelet recovery was 40.5 days (range, 24 to 120). A patient with myelodysplastic syndrome relapsed 8 months after transplant and died 4 months later; another patient with acute lymphoblastic leukemia relapsed after a 2 years follow-up. All remaining patients are alive and survive disease-free after a median follow-up of 30.5 months (range, 2 to 120) from transplant. 4. Discussion and conclusion UCB from sibling donors represents a suitable alternative to bone marrow for transplantation and collecting UCB is particularly indicated for patients needing a transplant on urgency. Indeed, provided that an adequate number of cells have been collected and cryopreserved, UCB from an HLA-identical family donor appears to be a proper source of stem cells for HCT mostly when time to proceed to transplant can be crucial for the success of the transplant itself. Furthermore, UCB transplant can avoid the discomfort caused by the bone marrow harvesting. Actually, medical indication for related UCB collection is limited to families with children in the donor's family suffering from a disease potentially curable by allogeneic HCT; in these situations family-directed
Table 2 Donors' characteristics. Characteristics
3. Results This study included a total of 187 pediatric patients and a total of 204 UCB collections. All UCB samples were collected by fully trained obstetricians and midwives in 6 collection sites. All planned UCB collections were successfully performed and a median volume of 75 ml excluding anticoagulant was collected (range 10–214.5 ml). All but one UCB samples were collected from full term deliveries. Most deliveries 118/204 (58%) were carried out by cesarean section, vaginal deliveries occurred in the remaining 86 cases (42%). In vaginal deliveries, the UCB units were always collected before placenta expulsion, whereas in cesarean sections the UCB was harvested both before and after placental delivery. All UCB samples were cryopreserved within 48 h from harvesting. No bacterial or fungi contamination was detected. UCB units main features are the following: the median total nucleated cell (TNC) count was 76.95 × 107 ranging from 10.0 to 305.2 × 107, the median CD34 + cell count and colony-forming unit granulocyte
Sex: Male/female Median gestational age, weeks (Range) Delivery type: VD/CS⁎ Median weight, grams (Range) HLA matching with recipient 6/6 5/6 4/6 3/6 b3/6 Not evaluable Not typed yet Total ⁎ VD: vaginal delivery; CS: cesarean section.
99/105 38 (33–41) 86/118 3255 (1320–4430) 27 0 2 31 28 64 52 204
M. Screnci et al. / Blood Cells, Molecules and Diseases 57 (2016) 71–73
Funding sources
Table 3 Characteristics of transplanted patients. Characteristics Age (yy) Body weight (kg) Gender (male/female) Diagnosis: Malignant hematological diseases Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Myelodysplastic syndrome Chronic Myeloid Leukemia Non malignant hematological diseases Thalassemia major Blackfan–Diamond anemia Aplastic anemia Sickle cell disease Immunodeficiency Disease Leukocyte adhesion deficiency Total
73
N
Median
(Range)
5 21
(3–11) (10–37)
None. Author contributions
11/4 6 1 2 2 1 8 5 1 1 1 1 1 15
UCB collection should be recommended. In this regard, our 20-year experience about the sibling cord blood donor program for HCT has allowed 15 patients to be transplanted. However, to date the usage rate of UCB collections has been rather low amounting to 7.4%. Indeed, in most cases the UCB collection was requested by clinicians even though patient's disease status did not require a transplant at that time. The medical decision to transplant the family-directed UCB unit was based on patient's disease status, HLA compatibility degree and UCB collection main features. Sometimes, the low cellular content of UCB units could represent a limitation to its use and collection bone marrow cells from the same donor to infuse along with the UCB has been proved to be an approach to increase cell dose [9]. In this regard, no UCB unit was deemed unsuitable for transplantation because of its main biological features. More recently some authors have illustrated novel and exciting role for UCB [10] other than in the transplantation setting. Furthermore, some investigation in the immunotherapy and regenerative medicine areas are ongoing and the results of studies in progress could expand indication for family directed UCB collection. Finally, a multicentric evaluation could be useful to better evaluate either the usage rate of this human resource or the cost-effective assessment; this analysis could be helpful to better establish a program for family-directed UCB banking in the next future. In view of these results and of possible future strategies, directeddonor family banking activities aimed at optimizing the cryopreservation and storage of UCB of a newborn sibling should be encouraged and closely monitored to ensure that common standards are followed.
MS drafted the manuscript, EM acquired and analyzed the data, AT VV FC EBA coordinated UCB collection and banking, SS MGP performed UCB and data collections, GG critically revised the manuscript. All authors revised the paper. Conflicts of interest The authors declare no potential conflicts of interest. Acknowledgments The authors thank all the UCB collection and processing personnel who collaborated in this study. References [1] K.K. Ballen, E. Gluckman, H.E. Broxmeyer, Umbilical cord blood transplantation: the first 25 years and beyond, Blood 122 (2013) 491–498. [2] F. Bernaudin, G. Socie, M. Kuentz, S. Chevret, M. Duval, et al., Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease, Blood 110 (2007) 2749–2756. [3] A.-L. Herr, N. Kabbara, C.M.S. Bonfim, P. Teira, F. Locatelli, et al., Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT, Blood 116 (2010) 1849–1856. [4] F. Locatelli, N. Kabbara, A. Ruggeri, A. Ghavamzadeh, I. Roberts, et al., Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling, Blood 122 (2013) 1072–1078. [5] K.M. Page, S. Parikh, K. J, Results of Cord Blood Transplantation in Children With Nonmalignant Hematologic Conditions, in: K. Ballen (Ed.), Umbilical Cord Blood Banking and Transplantation, Stem Cell Biology and Regenerative Medicine 2014, pp. 85–106, http://dx.doi.org/10.1007/978-3-319-06444-4_7. [6] J. Smythe, S. Armitage, D. McDonald, D. Pamphilon, M. Guttridge, et al., Directed sibling cord blood banking for transplantation: the 10-year experience in the national blood service in England, Stem Cells 25 (2007) 2087–2093. [7] E. Gluckman, A. Ruggeri, V. Rocha, E. Baudoux, M. Boo, et al., Family-directed umbilical cord blood banking, Haematologica 96 (2011) 1700–1707. [8] M. Screnci, E. Murgi, A. Tamburini, M.R. Pecci, G. Ballatore, et al., Family directed umbilical cord blood banking for acute leukemia: usage rate in hematopoietic stem cell transplantation, Stem Cell Rev. 11 (2015) 275–279. [9] L. Tucunduva, F. Volt, R. Cunha, F. Locatelli, et al., Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases, Br. J. Haematol. 169 (2015) 103–110. [10] N. Shah, J.J. Boelens, Umbilical cord blood: advances and opportunities, Cytotherapy 17 (2015) 693–694.
Contents lists available at ScienceDirect
Blood Cells, Molecules and Diseases journal homepage: www.elsevier.com/locate/bcmd
Short Communication
Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank Maria Screnci a,⁎, Emilia Murgi a, Veronica Valle a, Anna Tamburini b, Maria Grazia Pellegrini c, Sabrina Strano d, Francesca Corona a, Eleonora Barbacci Ambrogi a, Gabriella Girelli a a
Immunohaematology and Transfusion Medicine Unit, Azienda Policlinico Umberto I, Via Chieti N 7, 00161 Rome, Italy Immunohaematology and Transfusion Medicine Unit, Ospedale S. Eugenio, P.le dell'Umanesimo n10, 00144 Rome, Italy Obstetrics and Gynecology Unit, Ospedale S Giovanni Calibita, Piazza Fatebenefratelli n2, 00186 Rome, Italy d Obstetrics and Gynecology Unit, Ospedale S Pertini, Via dei Monti Tiburtini n 385, 00157 Rome, Italy b c
a r t i c l e
i n f o
Article history: Submitted 24 November 2015 Revised 22 December 2015 Accepted 29 December 2015 Available online 3 January 2016 Editor: Mohandas Narla Keywords: Alternative donor Related cord blood banking Family-directed cord blood banking Umbilical cord blood transplantation Stem cell transplantation
a b s t r a c t Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a “Sibling cord blood donor program for hematopoietic cell transplantation”. Here we report results of this project started 20 years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Hematopoietic cell transplantation (HCT) is the main curative treatment in patients with malignant and non malignant hematological disorders or genetic diseases, such as immunodeficiencies, inherited metabolic diseases and other conditions, who may benefit from a human leucocyte antigen (HLA) matched sibling donor. As umbilical cord blood (UCB) is a graft source [1] and UCB transplantation from HLA-identical sibling provides good results in children [2–5], then family directed UCB collection and banking is recommended in presence of medical indication for related UCB transplantation in a donor's sibling, particularly for patients in urgent need for transplantation who cannot wait for the donor's sibling bone marrow to be collected [6–8]. With the aim to provide access to all patients in need, in 1994 we started a “Sibling cord blood donor program for HCT”. All families entered into the study were experiencing a pregnancy and already caring for, or at high risk to have, a child with disease treatable by allogeneic HCT. Six
⁎ Corresponding author. E-mail addresses: [email protected], [email protected] (M. Screnci), [email protected] (A. Tamburini), [email protected] (M.G. Pellegrini), [email protected] (S. Strano).
http://dx.doi.org/10.1016/j.bcmd.2015.12.010 1079-9796/© 2016 Elsevier Inc. All rights reserved.
hospitals collaborated to this program. Herein we report our twenty year single center experience. 2. Patients and methods Data were obtained over a 20 years period between 1994 and 2014. As December 2014, a total of 194 families were enrolled for related UCB harvesting and cryostorage. Nine families were recruited more than once and potentially candidate to 19 UCB collections: in these cases, the patients were considered only once, at first collection's date. Patients' characteristics are detailed in Table 1. Seven families were recruited because of at high risk to have a child with disease treatable by HCT: both parents β thalassemia trait carriers and healthy or β thalassemia trait carrier newborn. The UCB procurements were mostly required by referring clinicians for patients with hematological malignancies (69%). Among malignancies, acute lymphoblastic leukemia was the most common diagnosis, while thalassemia major was the most frequent disease among non malignant conditions. Since according to applicable governmental rules family-directed UCB collection and storage are under the responsibility of public CB banks, then all families were addressed to UCB collection sites already collaborating in unrelated UCB donation and banking. Therefore,
72
M. Screnci et al. / Blood Cells, Molecules and Diseases 57 (2016) 71–73
Table 1 Patients' Characteristics. Characteristics Age (yy) Body weight (kg) at UCB collection Gender (male/female) Diagnosis: Malignant hematological diseases Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Myelodysplastic syndrome Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Chronic Myeloid Leukemia Non malignant hematological diseases Thalassemia major Blackfan–Diamond anemia Aplastic anemia Sickle cell disease Fanconi anemia Other Solid tumors Immunodeficiency diseases Metabolic diseases Other conditions Total
N
Median
(Range)
5.5 21
(1–17) (6–72)
112/75 129 91 13 10 9 2 4 38 14 8 5 5 1 5 9 5 1 5 187
standardized UCB collection, labeling, storage and shipment operating procedures were well known to all the involved personnel of the collection facilities. No family was charged for UCB collection or banking. With reference to local rules, written informed consent was obtained from the donor mother before delivery, as well as consent for confidential information, mandatory infectious testing, tissue typing and storage of units. Testing for infectious disease was performed on mother's serum and the screening included hepatitis B virus (HBV) surface antigen, antibodies to hepatitis C virus (HCV), HIV 1–2, and syphilis. Afterwards, since 2004 nucleic acid testing (NAT) was added to screen HCV, HIV and HBV. To prevent cell loss, all UCB collections were cryopreserved without volume reduction manipulation: cryoprotectant solution was prepared from dimethyl sulfoxide (DMSO) and human albumin to reach a final DMSO concentration of 10%. UCB units were frozen by controlled rate freezer and then transferred into liquid nitrogen based storage tanks, maintained at less than −150 °C and continuously monitored. To screen the collected UCB for transplantation suitability, cell and progenitor content evaluation, microbiological testing, red blood cells phenotype and HLA typing were carried out. HLA matching between patient and UCB donor was based on serological or molecular class I HLA typing and high resolution molecular class II typing. A descriptive analysis was made: the data are presented as absolute values, percentages, median values and range.
macrophage (CFU-GM) content were 2.3 × 106 (range 0.03– 17.2 × 106) and 4.76 × 105 (range 0.3–37.9 × 105) respectively. As detailed in Table 2, to date, HLA typing has been performed for 152 UCB collections while for 52 is pending: since 64 potential recipients have not been typed yet, HLA compatibility degree is evaluable only for 88 donor/recipient pairs and as expected about a third of UCBs resulted HLA identical to the intended recipient. Since the beginning of the program, the UCB collections have reached a median storage time of 7.8 years (range 0.1–20.3 years) and a total of 15 units has been transplanted. Considering HLA-identical donor/recipient pairs, a total of 15 patients (55.5%) were grafted with the intended fully matched UCB unit; most patients (53%) received UCB in conjunction with a small volume of bone marrow from the same HLA-identical sibling donor. Table 3 gives an overview of the transplanted patients. UCB units have been grafted after a median time of storage of 12 months (range 3–49 months). Biological characteristics of transplanted UCB units are summarized as follows: the median TNC count was 88.2 × 107 ranging from 38.3 to 203.3 × 107, the median CD34 + cell count and CFU-GM content were 2.0 × 106 (range 0.6– 9.4 × 106) and 3.5 × 105 (range 0.9–14.5 × 105) respectively. All evaluable patients engrafted, a patient with acute myeloid leukemia died 10 days after transplantation. For patients who engrafted, the median time to neutrophil recovery after transplant was 22.5 days (range, 17 to 45). The median time to platelet recovery was 40.5 days (range, 24 to 120). A patient with myelodysplastic syndrome relapsed 8 months after transplant and died 4 months later; another patient with acute lymphoblastic leukemia relapsed after a 2 years follow-up. All remaining patients are alive and survive disease-free after a median follow-up of 30.5 months (range, 2 to 120) from transplant. 4. Discussion and conclusion UCB from sibling donors represents a suitable alternative to bone marrow for transplantation and collecting UCB is particularly indicated for patients needing a transplant on urgency. Indeed, provided that an adequate number of cells have been collected and cryopreserved, UCB from an HLA-identical family donor appears to be a proper source of stem cells for HCT mostly when time to proceed to transplant can be crucial for the success of the transplant itself. Furthermore, UCB transplant can avoid the discomfort caused by the bone marrow harvesting. Actually, medical indication for related UCB collection is limited to families with children in the donor's family suffering from a disease potentially curable by allogeneic HCT; in these situations family-directed
Table 2 Donors' characteristics. Characteristics
3. Results This study included a total of 187 pediatric patients and a total of 204 UCB collections. All UCB samples were collected by fully trained obstetricians and midwives in 6 collection sites. All planned UCB collections were successfully performed and a median volume of 75 ml excluding anticoagulant was collected (range 10–214.5 ml). All but one UCB samples were collected from full term deliveries. Most deliveries 118/204 (58%) were carried out by cesarean section, vaginal deliveries occurred in the remaining 86 cases (42%). In vaginal deliveries, the UCB units were always collected before placenta expulsion, whereas in cesarean sections the UCB was harvested both before and after placental delivery. All UCB samples were cryopreserved within 48 h from harvesting. No bacterial or fungi contamination was detected. UCB units main features are the following: the median total nucleated cell (TNC) count was 76.95 × 107 ranging from 10.0 to 305.2 × 107, the median CD34 + cell count and colony-forming unit granulocyte
Sex: Male/female Median gestational age, weeks (Range) Delivery type: VD/CS⁎ Median weight, grams (Range) HLA matching with recipient 6/6 5/6 4/6 3/6 b3/6 Not evaluable Not typed yet Total ⁎ VD: vaginal delivery; CS: cesarean section.
99/105 38 (33–41) 86/118 3255 (1320–4430) 27 0 2 31 28 64 52 204
M. Screnci et al. / Blood Cells, Molecules and Diseases 57 (2016) 71–73
Funding sources
Table 3 Characteristics of transplanted patients. Characteristics Age (yy) Body weight (kg) Gender (male/female) Diagnosis: Malignant hematological diseases Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Myelodysplastic syndrome Chronic Myeloid Leukemia Non malignant hematological diseases Thalassemia major Blackfan–Diamond anemia Aplastic anemia Sickle cell disease Immunodeficiency Disease Leukocyte adhesion deficiency Total
73
N
Median
(Range)
5 21
(3–11) (10–37)
None. Author contributions
11/4 6 1 2 2 1 8 5 1 1 1 1 1 15
UCB collection should be recommended. In this regard, our 20-year experience about the sibling cord blood donor program for HCT has allowed 15 patients to be transplanted. However, to date the usage rate of UCB collections has been rather low amounting to 7.4%. Indeed, in most cases the UCB collection was requested by clinicians even though patient's disease status did not require a transplant at that time. The medical decision to transplant the family-directed UCB unit was based on patient's disease status, HLA compatibility degree and UCB collection main features. Sometimes, the low cellular content of UCB units could represent a limitation to its use and collection bone marrow cells from the same donor to infuse along with the UCB has been proved to be an approach to increase cell dose [9]. In this regard, no UCB unit was deemed unsuitable for transplantation because of its main biological features. More recently some authors have illustrated novel and exciting role for UCB [10] other than in the transplantation setting. Furthermore, some investigation in the immunotherapy and regenerative medicine areas are ongoing and the results of studies in progress could expand indication for family directed UCB collection. Finally, a multicentric evaluation could be useful to better evaluate either the usage rate of this human resource or the cost-effective assessment; this analysis could be helpful to better establish a program for family-directed UCB banking in the next future. In view of these results and of possible future strategies, directeddonor family banking activities aimed at optimizing the cryopreservation and storage of UCB of a newborn sibling should be encouraged and closely monitored to ensure that common standards are followed.
MS drafted the manuscript, EM acquired and analyzed the data, AT VV FC EBA coordinated UCB collection and banking, SS MGP performed UCB and data collections, GG critically revised the manuscript. All authors revised the paper. Conflicts of interest The authors declare no potential conflicts of interest. Acknowledgments The authors thank all the UCB collection and processing personnel who collaborated in this study. References [1] K.K. Ballen, E. Gluckman, H.E. Broxmeyer, Umbilical cord blood transplantation: the first 25 years and beyond, Blood 122 (2013) 491–498. [2] F. Bernaudin, G. Socie, M. Kuentz, S. Chevret, M. Duval, et al., Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease, Blood 110 (2007) 2749–2756. [3] A.-L. Herr, N. Kabbara, C.M.S. Bonfim, P. Teira, F. Locatelli, et al., Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT, Blood 116 (2010) 1849–1856. [4] F. Locatelli, N. Kabbara, A. Ruggeri, A. Ghavamzadeh, I. Roberts, et al., Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling, Blood 122 (2013) 1072–1078. [5] K.M. Page, S. Parikh, K. J, Results of Cord Blood Transplantation in Children With Nonmalignant Hematologic Conditions, in: K. Ballen (Ed.), Umbilical Cord Blood Banking and Transplantation, Stem Cell Biology and Regenerative Medicine 2014, pp. 85–106, http://dx.doi.org/10.1007/978-3-319-06444-4_7. [6] J. Smythe, S. Armitage, D. McDonald, D. Pamphilon, M. Guttridge, et al., Directed sibling cord blood banking for transplantation: the 10-year experience in the national blood service in England, Stem Cells 25 (2007) 2087–2093. [7] E. Gluckman, A. Ruggeri, V. Rocha, E. Baudoux, M. Boo, et al., Family-directed umbilical cord blood banking, Haematologica 96 (2011) 1700–1707. [8] M. Screnci, E. Murgi, A. Tamburini, M.R. Pecci, G. Ballatore, et al., Family directed umbilical cord blood banking for acute leukemia: usage rate in hematopoietic stem cell transplantation, Stem Cell Rev. 11 (2015) 275–279. [9] L. Tucunduva, F. Volt, R. Cunha, F. Locatelli, et al., Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases, Br. J. Haematol. 169 (2015) 103–110. [10] N. Shah, J.J. Boelens, Umbilical cord blood: advances and opportunities, Cytotherapy 17 (2015) 693–694.