- Email: [email protected]
Trends in hematopoietic stem cell transplant activity in Lebanon
HEMONC 177 19 June 2017 Hematol Oncol Stem Cell Ther (2017) xxx, xxx– xxx
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Available at www.sciencedirect.com
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Trends in hematopoietic stem cell transplant activity in Lebanon Ali Bazarbachi a,*, Ammar Zahreddine a,b, Radwan Massoud a, Jean Cheikh a, Colette Hanna c, Fadi Nasr c, Miguel Abboud d, Ahmad Ibrahim e
15
a Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon b Nursing Services, American University of Beirut Medical Center, Beirut, Lebanon c Division of Hematology and Oncology, Mount Lebanon Hospital, Baabda, Lebanon d Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, American University of Beirut, Beirut, Lebanon e Department of Internal Medicine, Division of Hematology and Oncology, Makassed General Hospital, Beirut, Lebanon
16
Received 17 January 2017; accepted 1 March 2017
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KEYWORDS Allogeneic stem cell transplantation; Autologous stem cell transplantation; Hematopoietic stem cell transplantation; Lebanon
Abstract Hematopoietic stem cell transplantation (HSCT) has been accessible to the population residing in Lebanon and surrounding countries since 1997. HSCT programs were developed in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital. Mount Lebanon Hospital initiated an autologous HSCT activity later. Between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT. Overall, autologous HSCT activity has remained stable over the past 5 years, whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 followed by a modest increase later. Haploidentical transplantation has mushroomed and represented almost half of allogeneic HSCT activity in 2016. AUBMC and Makassed General Hospital are members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation groups, and AUBMC has been accredited by JACIE (Joint Accreditation Committee – ISCT & EBMT) since 2016. The past 5 years have seen an increase in HSCT-related research and publications, mainly
* Corresponding author at: Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Medical Center, P.O. Box 113-6044, Beirut, Lebanon. E-mail address: [email protected] (A. Bazarbachi). http://dx.doi.org/10.1016/j.hemonc.2017.05.003 1658-3876/Ó 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
HEMONC 177 19 June 2017
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A. Bazarbachi et al. from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and post-transplant maintenance therapy.
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Ó 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
49 45 46 47 48
Introduction
Ethical considerations
97
The collection of data was done through a specific spreadsheet that had no patient identifiers. There has been no need to check individual patients’ medical records to collect the data. Hence, patients’ privacy and the confidentiality of their records and health status remained intact.
98
80
Hematopoietic stem cell transplantation (HSCT) became available in Lebanon in 1997. It is accessible to the population residing in Lebanon, as well as the surrounding countries where HSCT is limited, including Syria, Iraq, Palestine, and for expatriates living in the Gulf Cooperation Council countries. Hence, Lebanon has taken a leading role since the late 1990s in developing HSCT programs in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital (MGH). Later, a third center in the suburbs of Beirut, Mount Lebanon Hospital, initiated an autologous HSCT activity. The Lebanese population has increased >3-fold in the past 55 years, from 1.8 million in 1960 to 5.8 million in 2015 [1]. According to the World Bank, Lebanon is one of the developing countries with a gross domestic product of $47 billion in 2015, achieving a significant increase from $3.3 billion in 1988 [2]. In 2014, the Human Development Index of Lebanon was ranked 67 by the United Nations Development Programme (UNDP) with a gross national income per capita of $16,509 [3]. This Human Development Index of 67 is considered a high rank on the UNDP list, and is between Oman (52) and Iran (69) [3]. According to UNDP, the mean life expectancy of the Lebanese population is 79.3 years [3]. Lebanon has recently seen a significant increase in the overall annual cancer incidence from 382 per 100,000 in 2003 to 470 per 100,000 in 2008 [4]. By the year 2018, the incidence rates are foreseen to be 636 cases per 100,000 [4]. Among hematological malignancies, lymphoma is one of the top five cancers that affect the population of Lebanon [4].
81
Materials and methods
82
Data collection
50
51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79
90
Data from the three Lebanese HSCT centers were collected retrospectively from the beginning of 2012 till the end of 2016 with regard to total number of transplants per year, distribution of patients by age group and diagnosis, type of transplant, type of donor, and stem cell source. A template for data collection was sent out to be filled in individually by the center coordinators or data owners, and collected into one dataset.
91
Participating centers
92
The three HSCT centers of Lebanon have participated in sharing their data. MGH and AUBMC cater for the needs of allogeneic and autologous HSCT patients. In addition, Mount Lebanon Hospital caters only for patients requiring autologous HSCT.
83 84 85 86 87 88 89
93 94 95 96
99 100 101 102
Results
103
Number of transplants
104
For the period between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT (Fig. 1A). Overall, autologous HSCT activity has remained stable over the past 5 years (Fig. 1B), whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 in both centers followed by a modest increase later (Fig. 1C). Over this 5-year period, the adult patient population represented 85.2% (764 patients), including 227 allogeneic HSCT and 537 autologous HSCT (Table 1). Conversely, the pediatric patient population represented 14.8% (133 patients) distributed between 76 allogeneic HSCT and 57 autologous HSCT (Table 1).
105
Type of disease
118
Allogeneic HSCT was predominantly performed for acute leukemia with acute myeloid leukemia representing 35% of allogeneic HSCT followed by acute lymphoblastic leukemia (18%). Other minor indications (Fig. 2A) were lymphoproliferative disorders (14%), predominantly Hodgkin’s and nonHodgkin’s lymphoma, bone marrow failure (14%), myelodysplasia (5%), chronic myeloid leukemia (5%), inherited metabolic disorders (5%), and immunodeficiency (4%). By contrast, autologous HSCT was mainly performed for plasma cell disorders (35%), Hodgkin’s (26%) or nonHodgkin’s (27%) lymphoma, and solid tumors (12%), mostly neuroblastoma, medulloblastoma, and germ cell tumors (Fig. 2B).
119
Type of donor and stem cell source
132
Even though matched related donors (MRDs) were and remain the major source for allogeneic HSCT, the past 5 years have seen an increase in haploidentical donor transplantation when an MRD was not available. Indeed, haploidentical donors started to be used as early as 2013 when this source represented 5% of allogeneic HSCT to reach 49% of allogeneic HSCT in 2016 (Fig. 3A). By contrast, the matched unrelated donor (MUD) program was initiated as early as 2011 using the National Marrow Donor Program
133
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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A
134 290 473 897
B
134 184 276 594
C
106 197 303
Fig. 1 HSCT activity in the three transplant centers in Lebanon (2012–2016). (A) Total transplant activity. (B) Autologous HSCT activity. (C) Allogeneic HSCT activity. Note. AUB = American University of Beirut; HSCT = hematopoietic stem cell transplantation; MGH = Makassed General Hospital; MLH = Mount Lebanon Hospital.
142 143 144 145 146 147 148 149 150
search through an agreement with AUBMC. However, from 2012 to 2016, only six MUD transplants were performed (5 adult and 1 pediatric; Fig. 3A). Finally, no umbilical cord blood source has been used. Peripheral blood stem cells represent the predominant source for allogeneic HSCT (55%), mostly in the adult population, and almost the exclusive source for autologous HSCT (Fig. 3B). Bone marrow harvesting still represents the predominant source for pediatric allogeneic HSCT (75%).
Participation of transplant registries
151
Both AUBMC and MGH are official members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation (EMBMT) groups. Both institutions annually report transplant data to the EBMT registry and transplant activity to EBMT and EMBMT. In Lebanon, there has not been any public registry for the MUD or the umbilical cord blood units. AUBMC has a signed
152
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A. Bazarbachi et al. Table 1 Annual Hematopoietic Stem Cell Transplantation Activity in Lebanon between 2012 and 2016, Distributed by Age Group and Type of Transplant.
2012 2013 2014 2015 2016 Total
Adult allogeneic
Pediatric allogeneic
Adult autologous
Pediatric autologous
Total
34 44 46 48 55 227
9 17 19 18 13 76
102 116 96 121 102 537
9 12 8 11 17 57
154 189 169 198 187 897
A
Lymphoproliferative disorders HL 56% NHL 35% CLL 6% PCD 3%
B
Solid tumors Neuroblastoma 47.17% Germ cell tumors 30.2% Brain Tumors 22.63%
Fig. 2 Distribution of HSCT patients in Lebanon (2012–2016) by diagnosis. (A) Allogeneic HSCT. (B) Autologous HSCT. Note. HSCT = hematopoietic stem cell transplantation.
159 160 161 162
agreement with NMDP that facilitates the search for MUDs. So far, six MUD allogeneic HSCTs have been performed since 2012. However, no umbilical cord blood unit has yet been utilized as part of the HSCT centers of Lebanon.
Quality management and accreditation
163
The HSCT program at AUBMC received its Joint Accreditation Committee – ISCT & EBMT (JACIE) accreditation in
164
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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Fig. 3 Distribution of allogeneic hematopoietic stem cell transplantation patients in Lebanon (2012–2016) by (A) type of donor or (B) source of stem cells.
166 167 168 169 170 171 172 173 174 175
August 2016. This was done after 3-years preparations and process streamlining by a multidisciplinary team of clinical and nonclinical staff who were devoted to make this accreditation status possible. A critical step was the implementation of an HSCT quality management program in 2013. The transplant unit at MGH is conducting the necessary preparations for pre-inspection checks, gap analysis with the standards, and for the development of their own quality management plan prior to a site visit by the JACIE inspectors.
176
Research activities
177
The past 5 years have seen an increase in HSCT-related research and publications, mainly from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and posttransplant maintenance therapy [5,6]. HSCT-related publications also included collaborative studies with EBMT or EMBMT members [7–10] or developing regional or international transplant guidelines [11,12]14]. Research activities are governed by an Institutional Review Board that oversees the ethical considerations of all research studies.
178 179 180 181 182 183 184 185 186
Discussion HSCT activity in Lebanon remains intermediate (340 HSCT per 10 million residents in 2015); lower than in Western Europe and North America. This is despite the fact that Lebanon attracts a significant number of regional patients. Except for a steep increase between 2012 and 2013, mainly for allogeneic HSCT, this activity has remained overall stable with a modest increase in the past few years. Challenges that hinder HSCT growth are mostly financial limitations for a significant percentage of the population in Lebanon and neighboring countries, as well as a fragmented practice of hematology in the country with a private practice culture that limits referral for transplant. Another limitation for allogeneic HSCT is the underrepresentation of the Middle East population in international donor registries, resulting in a low chance for finding an MUD when an MRD is not available. This limitation has been recently overcome by a steady increase in the number of haploidentical allogeneic HSCT, with numbers of haploHSCTs in 2016 close to that of MRDs. A recent trend in Lebanon was the use of reduced toxicity conditioning as preparative regimen for allogeneic HSCT,
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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which allowed patients >65 years of age, and those with comorbidity to be transplanted. Similarly, there has been an increase in the allogeneic HSCT performed on patients with lymphoma, whether they were refractory to chemotherapy or in relapse shortly after autologous HSCT. Sequential conditioning was introduced in 2015, allowing transplantation of patients with refractory leukemia or lymphoma.
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References
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[1] World Bank. Population, total. Lebanon. [Accessed December 30, 2016]. [2] World Bank. GDP per capita (current US$). [Accessed December 30, 2016]. [3] United Nations Development Program. Human development reports. [Accessed December 30, 2016]. [4] Shamseddine A, Saleh A, Charafeddine M, Seoud M, Mukherji D, Temraz S, et al. Cancer trends in Lebanon: a review of incidence rates for the period of 2003–2008 and projections until 2018. Popul Health Metrics 2014;12:4. [5] Antar A, Kharfan-Dabaja MA, Mahfouz R, Bazarbachi A. Sorafenib maintenance appears safe and improves clinical outcomes in FLT3-ITD acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Clin Lymphoma Myeloma Leuk 2015;15:298–302. http://dx.doi.org/10.1016/ j.clml.2014.12.005. [6] El Cheikh J, Otrock ZK, Qannus AA, Kharfan-Dabaja MA, Bazarbachi A. Risk-adapted approach to HLA-matched sibling hematopoietic cell allografting: impact of adjusting conditioning intensity and integrating post-transplant therapeutic interventions. Clin Lymphoma Myeloma Leuk 2016;16:304–10.
[7] Bazarbachi A, Labopin M, Ghavamzadeh A, Giebel S, Al-Zahrani H, Ladeb S, et al. Allogeneic matched-sibling hematopoietic cell transplantation for AML: comparable outcomes between Eastern Mediterranean (EMBMT) and European (EBMT) centers. Bone Marrow Transplant 2013;8:1065–9. [8] Bazarbachi A, Labopin M, Kharfan-Dabaja MA, Schwerdtfeger R, Volin L, Bourhis JH, et al. Allogeneic hematopoietic cell transplantation in acute myeloid leukemia with normal karyotype and isolated nucleophosmin-1 (NPM1) mutation: outcome strongly correlates with disease status. Haematologica 2016;101:e34–7. [9] Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Socie G, Kroeger N, Blaise D, et al. Higher busulfan dose intensity appears to improve leukemia-free and overall survival in AML allografted in CR2: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Leuk Res 2015;39:933–7. [10] Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Hamladji RM, Blaise D, Socie G, et al. Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 2014;49:1170–5. [11] Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2016;51:906–12. [12] Al Jefri AH, Abujazar H, Al-Ahmari A, Al Rawas A, Al Zahrani Z, Alhejazi A, et al. Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: middle East/North Africa regional consensus on prevention, diagnosis and management. Bone Marrow Transplant 2017;52:588–91.
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Available at www.sciencedirect.com
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journal homepage: www.elsevier.com/locate/hemonc
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Trends in hematopoietic stem cell transplant activity in Lebanon Ali Bazarbachi a,*, Ammar Zahreddine a,b, Radwan Massoud a, Jean Cheikh a, Colette Hanna c, Fadi Nasr c, Miguel Abboud d, Ahmad Ibrahim e
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a Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon b Nursing Services, American University of Beirut Medical Center, Beirut, Lebanon c Division of Hematology and Oncology, Mount Lebanon Hospital, Baabda, Lebanon d Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, American University of Beirut, Beirut, Lebanon e Department of Internal Medicine, Division of Hematology and Oncology, Makassed General Hospital, Beirut, Lebanon
16
Received 17 January 2017; accepted 1 March 2017
9 10 11 12 13 14
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27 28 19 29 20 30 21 31 22 32 23 33 24 34 25 35 26 36 37 38 39 40 41 42
KEYWORDS Allogeneic stem cell transplantation; Autologous stem cell transplantation; Hematopoietic stem cell transplantation; Lebanon
Abstract Hematopoietic stem cell transplantation (HSCT) has been accessible to the population residing in Lebanon and surrounding countries since 1997. HSCT programs were developed in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital. Mount Lebanon Hospital initiated an autologous HSCT activity later. Between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT. Overall, autologous HSCT activity has remained stable over the past 5 years, whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 followed by a modest increase later. Haploidentical transplantation has mushroomed and represented almost half of allogeneic HSCT activity in 2016. AUBMC and Makassed General Hospital are members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation groups, and AUBMC has been accredited by JACIE (Joint Accreditation Committee – ISCT & EBMT) since 2016. The past 5 years have seen an increase in HSCT-related research and publications, mainly
* Corresponding author at: Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Medical Center, P.O. Box 113-6044, Beirut, Lebanon. E-mail address: [email protected] (A. Bazarbachi). http://dx.doi.org/10.1016/j.hemonc.2017.05.003 1658-3876/Ó 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
HEMONC 177 19 June 2017
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A. Bazarbachi et al. from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and post-transplant maintenance therapy.
43 44
Ó 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
49 45 46 47 48
Introduction
Ethical considerations
97
The collection of data was done through a specific spreadsheet that had no patient identifiers. There has been no need to check individual patients’ medical records to collect the data. Hence, patients’ privacy and the confidentiality of their records and health status remained intact.
98
80
Hematopoietic stem cell transplantation (HSCT) became available in Lebanon in 1997. It is accessible to the population residing in Lebanon, as well as the surrounding countries where HSCT is limited, including Syria, Iraq, Palestine, and for expatriates living in the Gulf Cooperation Council countries. Hence, Lebanon has taken a leading role since the late 1990s in developing HSCT programs in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital (MGH). Later, a third center in the suburbs of Beirut, Mount Lebanon Hospital, initiated an autologous HSCT activity. The Lebanese population has increased >3-fold in the past 55 years, from 1.8 million in 1960 to 5.8 million in 2015 [1]. According to the World Bank, Lebanon is one of the developing countries with a gross domestic product of $47 billion in 2015, achieving a significant increase from $3.3 billion in 1988 [2]. In 2014, the Human Development Index of Lebanon was ranked 67 by the United Nations Development Programme (UNDP) with a gross national income per capita of $16,509 [3]. This Human Development Index of 67 is considered a high rank on the UNDP list, and is between Oman (52) and Iran (69) [3]. According to UNDP, the mean life expectancy of the Lebanese population is 79.3 years [3]. Lebanon has recently seen a significant increase in the overall annual cancer incidence from 382 per 100,000 in 2003 to 470 per 100,000 in 2008 [4]. By the year 2018, the incidence rates are foreseen to be 636 cases per 100,000 [4]. Among hematological malignancies, lymphoma is one of the top five cancers that affect the population of Lebanon [4].
81
Materials and methods
82
Data collection
50
51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79
90
Data from the three Lebanese HSCT centers were collected retrospectively from the beginning of 2012 till the end of 2016 with regard to total number of transplants per year, distribution of patients by age group and diagnosis, type of transplant, type of donor, and stem cell source. A template for data collection was sent out to be filled in individually by the center coordinators or data owners, and collected into one dataset.
91
Participating centers
92
The three HSCT centers of Lebanon have participated in sharing their data. MGH and AUBMC cater for the needs of allogeneic and autologous HSCT patients. In addition, Mount Lebanon Hospital caters only for patients requiring autologous HSCT.
83 84 85 86 87 88 89
93 94 95 96
99 100 101 102
Results
103
Number of transplants
104
For the period between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT (Fig. 1A). Overall, autologous HSCT activity has remained stable over the past 5 years (Fig. 1B), whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 in both centers followed by a modest increase later (Fig. 1C). Over this 5-year period, the adult patient population represented 85.2% (764 patients), including 227 allogeneic HSCT and 537 autologous HSCT (Table 1). Conversely, the pediatric patient population represented 14.8% (133 patients) distributed between 76 allogeneic HSCT and 57 autologous HSCT (Table 1).
105
Type of disease
118
Allogeneic HSCT was predominantly performed for acute leukemia with acute myeloid leukemia representing 35% of allogeneic HSCT followed by acute lymphoblastic leukemia (18%). Other minor indications (Fig. 2A) were lymphoproliferative disorders (14%), predominantly Hodgkin’s and nonHodgkin’s lymphoma, bone marrow failure (14%), myelodysplasia (5%), chronic myeloid leukemia (5%), inherited metabolic disorders (5%), and immunodeficiency (4%). By contrast, autologous HSCT was mainly performed for plasma cell disorders (35%), Hodgkin’s (26%) or nonHodgkin’s (27%) lymphoma, and solid tumors (12%), mostly neuroblastoma, medulloblastoma, and germ cell tumors (Fig. 2B).
119
Type of donor and stem cell source
132
Even though matched related donors (MRDs) were and remain the major source for allogeneic HSCT, the past 5 years have seen an increase in haploidentical donor transplantation when an MRD was not available. Indeed, haploidentical donors started to be used as early as 2013 when this source represented 5% of allogeneic HSCT to reach 49% of allogeneic HSCT in 2016 (Fig. 3A). By contrast, the matched unrelated donor (MUD) program was initiated as early as 2011 using the National Marrow Donor Program
133
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106 107 108 109 110 111 112 113 114 115 116 117
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A
134 290 473 897
B
134 184 276 594
C
106 197 303
Fig. 1 HSCT activity in the three transplant centers in Lebanon (2012–2016). (A) Total transplant activity. (B) Autologous HSCT activity. (C) Allogeneic HSCT activity. Note. AUB = American University of Beirut; HSCT = hematopoietic stem cell transplantation; MGH = Makassed General Hospital; MLH = Mount Lebanon Hospital.
142 143 144 145 146 147 148 149 150
search through an agreement with AUBMC. However, from 2012 to 2016, only six MUD transplants were performed (5 adult and 1 pediatric; Fig. 3A). Finally, no umbilical cord blood source has been used. Peripheral blood stem cells represent the predominant source for allogeneic HSCT (55%), mostly in the adult population, and almost the exclusive source for autologous HSCT (Fig. 3B). Bone marrow harvesting still represents the predominant source for pediatric allogeneic HSCT (75%).
Participation of transplant registries
151
Both AUBMC and MGH are official members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation (EMBMT) groups. Both institutions annually report transplant data to the EBMT registry and transplant activity to EBMT and EMBMT. In Lebanon, there has not been any public registry for the MUD or the umbilical cord blood units. AUBMC has a signed
152
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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A. Bazarbachi et al. Table 1 Annual Hematopoietic Stem Cell Transplantation Activity in Lebanon between 2012 and 2016, Distributed by Age Group and Type of Transplant.
2012 2013 2014 2015 2016 Total
Adult allogeneic
Pediatric allogeneic
Adult autologous
Pediatric autologous
Total
34 44 46 48 55 227
9 17 19 18 13 76
102 116 96 121 102 537
9 12 8 11 17 57
154 189 169 198 187 897
A
Lymphoproliferative disorders HL 56% NHL 35% CLL 6% PCD 3%
B
Solid tumors Neuroblastoma 47.17% Germ cell tumors 30.2% Brain Tumors 22.63%
Fig. 2 Distribution of HSCT patients in Lebanon (2012–2016) by diagnosis. (A) Allogeneic HSCT. (B) Autologous HSCT. Note. HSCT = hematopoietic stem cell transplantation.
159 160 161 162
agreement with NMDP that facilitates the search for MUDs. So far, six MUD allogeneic HSCTs have been performed since 2012. However, no umbilical cord blood unit has yet been utilized as part of the HSCT centers of Lebanon.
Quality management and accreditation
163
The HSCT program at AUBMC received its Joint Accreditation Committee – ISCT & EBMT (JACIE) accreditation in
164
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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Trends in hematopoietic stem cell
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Fig. 3 Distribution of allogeneic hematopoietic stem cell transplantation patients in Lebanon (2012–2016) by (A) type of donor or (B) source of stem cells.
166 167 168 169 170 171 172 173 174 175
August 2016. This was done after 3-years preparations and process streamlining by a multidisciplinary team of clinical and nonclinical staff who were devoted to make this accreditation status possible. A critical step was the implementation of an HSCT quality management program in 2013. The transplant unit at MGH is conducting the necessary preparations for pre-inspection checks, gap analysis with the standards, and for the development of their own quality management plan prior to a site visit by the JACIE inspectors.
176
Research activities
177
The past 5 years have seen an increase in HSCT-related research and publications, mainly from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and posttransplant maintenance therapy [5,6]. HSCT-related publications also included collaborative studies with EBMT or EMBMT members [7–10] or developing regional or international transplant guidelines [11,12]14]. Research activities are governed by an Institutional Review Board that oversees the ethical considerations of all research studies.
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Discussion HSCT activity in Lebanon remains intermediate (340 HSCT per 10 million residents in 2015); lower than in Western Europe and North America. This is despite the fact that Lebanon attracts a significant number of regional patients. Except for a steep increase between 2012 and 2013, mainly for allogeneic HSCT, this activity has remained overall stable with a modest increase in the past few years. Challenges that hinder HSCT growth are mostly financial limitations for a significant percentage of the population in Lebanon and neighboring countries, as well as a fragmented practice of hematology in the country with a private practice culture that limits referral for transplant. Another limitation for allogeneic HSCT is the underrepresentation of the Middle East population in international donor registries, resulting in a low chance for finding an MUD when an MRD is not available. This limitation has been recently overcome by a steady increase in the number of haploidentical allogeneic HSCT, with numbers of haploHSCTs in 2016 close to that of MRDs. A recent trend in Lebanon was the use of reduced toxicity conditioning as preparative regimen for allogeneic HSCT,
Please cite this article in press as: Bazarbachi A et al., Trends in hematopoietic stem cell transplant activity in Lebanon ..., Hematol Oncol Stem Cell Ther (2017), http://dx.doi.org/10.1016/j.hemonc.2017.05.003
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which allowed patients >65 years of age, and those with comorbidity to be transplanted. Similarly, there has been an increase in the allogeneic HSCT performed on patients with lymphoma, whether they were refractory to chemotherapy or in relapse shortly after autologous HSCT. Sequential conditioning was introduced in 2015, allowing transplantation of patients with refractory leukemia or lymphoma.
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References
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[1] World Bank. Population, total. Lebanon.
[7] Bazarbachi A, Labopin M, Ghavamzadeh A, Giebel S, Al-Zahrani H, Ladeb S, et al. Allogeneic matched-sibling hematopoietic cell transplantation for AML: comparable outcomes between Eastern Mediterranean (EMBMT) and European (EBMT) centers. Bone Marrow Transplant 2013;8:1065–9. [8] Bazarbachi A, Labopin M, Kharfan-Dabaja MA, Schwerdtfeger R, Volin L, Bourhis JH, et al. Allogeneic hematopoietic cell transplantation in acute myeloid leukemia with normal karyotype and isolated nucleophosmin-1 (NPM1) mutation: outcome strongly correlates with disease status. Haematologica 2016;101:e34–7. [9] Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Socie G, Kroeger N, Blaise D, et al. Higher busulfan dose intensity appears to improve leukemia-free and overall survival in AML allografted in CR2: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Leuk Res 2015;39:933–7. [10] Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Hamladji RM, Blaise D, Socie G, et al. Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 2014;49:1170–5. [11] Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2016;51:906–12. [12] Al Jefri AH, Abujazar H, Al-Ahmari A, Al Rawas A, Al Zahrani Z, Alhejazi A, et al. Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: middle East/North Africa regional consensus on prevention, diagnosis and management. Bone Marrow Transplant 2017;52:588–91.
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