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Bone marrow transplantation was the term origillnally used to describe the collection and transllplantation of hematopoietic stem cells from the

bone marrow, but with the recent demonstration that the peripheral blood and umbilical cord blood are also useful sources of stem cells, hematopoietic stem cell transplantation (HSCT) has become the preferred generic term. The procedure is usually carried out for one of two purposes: (1) to replace an abnormal but nonmalignant lymphohematopoietic system with one from a normal donor, or (2) to treat malignancy by allllowing the administration of higher doses of myelosupllpressive therapy than would otherwise be possible. The use of bone marrow transplantation has been steadily increasing, both because of its demonstrated effectivellness in selected diseases and because of the increasing availability of donors. The International Bone Marrow Transplant Registry estimates that about 50 000 transll

Hematopoietic stem cell transplantation in Iran: 1991 to 2008

from the hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, dr. shariati hospital, tehran, iran

correspondence: farnaz Khatami md · hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran · bmtcontact@sina.tums.ac.ir · accepted for publication: march 2008

hematol oncol stem cel ther 2008; 1(4): 231-238

Ardeshir Ghavamzadeh, Kamran Alimogaddam, Mohammad Jahani, Seyedasadollah Mousavi, Masoud Iravani, Babak Bahar, Ali Khodabandeh, Farnaz Khatami, Arash Jalali

since 1991, 2042 first hematopoietic stem cell transplants (hsct) have been performed at the hematology-oncology and stem cell transplantation research center at tehran university of medical sciences. acute myelogenous leukemia (548 patients), thalassemia major (335 patients) and acute lymphoblastic leukemia (275 patients) have been the most common transplanted disorders. there were 1418 cases that received allogeneic hsct and 624 cases that have received autologous hsct. the numbers of alloge--neic and autologous hsct have increased, but the allogeneic to autologous ratio has remained con--stant. the first peripheral blood hematopoietic stem cell transplantation was performed in 1996; since then, 1671 have been done. the donor types for 1418 allogeneic first hsct were 1367 (96.4%) human leukocyte antigen (hla) matched-identical siblings, 29 (2%) hla-mismatched sibling/other relative, 13 (0.9%) syngeneic twins, 5 (0.4%) hla-matched other relatives and 4 (0.3%) unrelated. the first cord blood hematopoietic stem cell transplantation was performed in 1998 and since then there have been 14 patients that have obtained cord blood transplantations. recently, new methods have been used like donor lymphocyte infusion (dli) and cellular therapy. there were 111 patients with cellular therapy for post-myocardial infarction, cirrhosis, thalassemia major, multiple sclerosis, head of femur necrosis and renal cell carcinoma.

plants are performed each year.1, 2

The HematologylOncology and Stem Cell Transplantation Research Center at Tehran University of Medical Sciences is located in Shariati Hospital. The first HSCT was performed by Professor Ghavamzadeh and colleagues in 1991, who have continued to carry out this treatment for different kinds of cancers and hemoglobical disorders. The center is a member of the International Blood and Marrow Transplantation Registry (IBMTR) and the European of Blood and Marrow Transplantation Registry (EBMTR). In asllsociation with these organizations, the center collects data on patients who have undergone transplantation and cooperates with these centers in various scientific and research fields. This center is a member of Asian Pacific Cancer Center (APCC) and also has collabollrations with blood and cancer associations such as the American Society of Hematology (ASH), the

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International Society of Hematology (ISH), and the European School of Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and other centers. The plans and aims include expansion of cytogenetic and molecular biological diagnostic tests, establishment of a cord blood bank and development of research activities in these fields.3

PATIenTS AnD MeThODS Stem cell sources for patients underwent HSCT in the HematologylOncology and Stem Cell Transplantation Research Center from March 1991 to December 2007 were bone marrow, peripheral blood, cord blood, comllbining bone marrow and peripheral blood, and mesllenchymal origins. Depending on the condition of the patient, we used allogeneic, autologous or syngeneic stem cell grafts.4 All patients were treated in completely isolated rooms during the peritransplant period. These were conventional rooms that were private and HEPAlfiltered with home entertainment appliances to avoid depression. Stem cells were obtained and kept at 4ºC for 1 to 4 days before reinfusion. The stem cells were reinfused without purging.5 The center has a research office with a data management section that gathers the stem cell transplantation data from stem cell transplanlltation wards, checking reports for completeness of data and identifying missing data, correcting missing fields,

and entering report forms into the computer database program (Software version 3.2.4 that meets the needs of HSCT centers) for statistical analysis and preparation of statistical reports, finally sending them to CIBMTR. The office is also responsible for quality control of the data entry processes and training patients and stem cell transplantation and data management staff. In Iran, which has a population of about 70 million people, the incidence of transplantable diseases is estimated at about 2 per 100 000 or 1400 patients per year. The cost of transplant procedures is borne by insurance compallnies and the board of trustees.

The number of HSCTs indicates the number of palltients treated for the first time with HSCT. The transllplant rate is defined as the number of HSCTs per 1 millllion inhabitants.6 Population data were obtained from the Statistical Center of Iran (www.sci.org.ir). Reltransllplant was defined as an unplanned HSCT for rejeclltion or relapse after a first HSCT. Donor lymphocyte infusion (DLI) is a method for treatment of patients with recurrent or persistent malignancy after allogeneic HSCT with infusion of additional lymphocytes oblltained from the original donor, without the cover of imllmunosuppressive agents.7 Cell therapy is a technology that relies on replacing diseased or dysfunctional cells with healthy, functioning ones.

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

12

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Figure 1. Number of first hematopoietic stem cell transplantations from 1991 to 2007.

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1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Rate

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Figure 2. Total rate per million of first hematopoietic stem cell transplantations during the past 17 years.

Figure 3. Number of allogeneic and autologous hematopoietic stem cell transplantations.

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Figure 5. Number of peripheral blood and bone marrow hematopoietic stem cell transplantations.

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Figure 4. Standardized rate of allogeneic and autologous hematopoietic stem cell transplantations in the past 17 years.

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1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

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Figure 7. Hematopoietic stem cell transplantation number for thalassemia patients.

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Figure 6. Hematopoietic stem cell transplantation number by graft type for aml patients (upper). Standardized number of allogeneic and autologous hematopoietic stem cell transplantations for aml patients (lower).

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1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

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Figure 8. evaluation of hematopoietic stem cell transplantation number by graft type for all patients.

Table 1. Number of patients with a first hematopoietic stem cell transplantation listed by disease.

Specific diseaseGraft type

TotalAutologous Allogeneic

acute myelogenous leukemia 190 358 548

acute lymphoblastic leukemia 25 250 275

Other leukemia 7 7

Cml 222 222

multiple myeloma 158 3 161

plasma cell disorder 7 1 8

lymphomas 205 33 238

Solid tumors 35 6 41

Severe aplastic anemia 125 125

Thalassemia major 335 335

inherited abnormalities of RBC 29 29

auto-immune diseases 4 0 4

inherited disorder of metabolism 3 3

Disorder of immune system 13 13

Histiocytic disorders 1 1

mDS/mpS 32 32

Total 624 1418 2042

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ReSULTSThe first stem cell transplantation was performed on 31 March 1991. From then until 31 December 2007, a tolltal of 2042 first HSCTs have been carried out (Figure 1). The number of HSCTs increased tenfold in the 2000s compared to last decade. The HSCT rate during the past 17 years was 32.6 transplants per one million inhabitants and the rate per million has increased from 1991 to 2008 (Figure 2). Of 2042 first transplantalltions, 1418 (69%) were allogeneic and 624 (31%) were autologous HSCT (Figure 3). The number of allogenellic and autologous HSCT increased, but the allogeneic to autologous ratio remained constant (Figure 4). Of 1418 allogeneic first HSCT, there were 1101 (77%) pellripheral blood, 281 (20%) bone marrow, 6 (0.5%) comllbined peripheral blood and bone marrow and 16 (1.5%) mesenchymal with bone marrow or peripheral blood as stem cell sources. Of 624 autologous patients with first HSCT, 556 (89%) received peripheral blood, 65 (10%) bone marrow and 1% mixed bone marrow and periphlleral blood as stem cell sources (Figure 5).

The donor types for 1418 allogeneic first HSCT were 1367 (96.4%) HLAlmatched identical siblings, 29 (2%) HLAlmismatched siblings/other relatives, 13 (0.9%) syngeneic twins, 5 (0.4%) HLAlmatched other relatives and 4 (0.3%) unrelated. The first cord blood HSCT was performed in 1998 and since then there 14 patients have obtained cord blood transplantations. The most cord blood transplantations were in 2004. All of the cord blood HSCT was allogeneic and there was no autologous cord blood HSCT.

The main diseases for which transplant were perllformed are shown in 1 1.8 Allogeneic HSCT was more common than autologous HSCT in acute myelogenous leukemia and acute lymphoblastic leukemia patients. Patients with lymphomas, multiple myeloma, plasma cell disorders and solid tumors received autologous HSCT more frequently. On the other hand, patients with chronic myelogenous leukemia, severe aplastic anemia, hemoglobinopathies, disorders of the imllmune system, myelodysplasia and inherited disorders of metabolism were treated with allogeneic HSCT. Autoimmune diseases were the only indication for only autologous HSCT. Acute myelogenous leukemia, thalassemia major and acute lymphoblastic leukemia were the most common transplanted disorders.9 Acute myelogenous leukemia showed a fixed increase in both allogeneic and autologous HSCT (Figure 6a) and the allogeneic to autologous ratio was stable (Figure 6b).

HSCT for thalassemia major peaked in 2001 then declined rapidly until 2006. Afterward, the number of cases increased (Figure 7). HSCT for acute lymphoblaslltic leukemia initially started with autologous HSCT in 1991. This was augmented by allogeneic HSCT beginllning in 1995, and thereafter there was an increase in allllogeneic HSCT with stable low numbers for autologous HSCT (Figure 8). Ninety patients received donor lymllphocyte infusion (DLI). Some patients obtained DLI more than once. The total number of DLI procedures was 128 with the highest frequency in 2006. During the past 17 years, 30 patients were retransplanted. The common disorders in retransplanted patients were thalllassemia major, acute myelogenous leukemia, lymphollmas and severe aplastic anemia. Cellular therapy was done in 111 patients, 41 patients were postlmyocardial infarction, 27 had cirrhosis, 20 had thalassemia major, 11 had multiple sclerosis, 11 had head of femur necrosis and 1 patient had renal cell carcinoma.

DISCUSSIOnHematopoietic stem cell transplantation is the choice of treatment for many malignant, nonmalignant and genetic diseases. Based on a review of statistics during the past 17 years in HematologylOncology and Stem Cell Transplantation Research Center, the number and rate HSCT have developed considerably, especially afllter the year 2000. It is notable that the transplant rate for allogeneic HSCT was more than for autologous HSCT, but both have increased with a stable ratio. The number of HSCTs for acute myelogenous leukemia and acute lymphoblastic leukemia was most frequent amongst all disorders; the predominant type of HSCT for these diseases was allogeneic, which is similar to the EBMT (European Group for Blood and Marrow Transplantation) survey.10 Peripheral blood was the main source of HSCT as it was in the EBMT survey.11 The most frequent donor type was allogeneic full HLAlmatched sibling. Future plans in this center include studies of transplants for breast cancer, neuroblastoma, Ewing sarcoma, soft tissue sarcoma, allogeneic HSCT for renal cell cancer, allogeneic HSCT for colorectal carcinoma and also cell therapies for postlmyocardial infarction, cirrhosis, thalassemia major, multiple sclerollsis, head of femur necrosis, severe aplastic anemia and renal cell carcinoma.

AcknowledgmentsThe collaboration of all colleagues is appreciated.

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