- Email: [email protected]
National survey of hemapheresis practice in Turkey (1998)
Transfusion Science 22 (2000) 195±201
www.elsevier.com/locate/transci
National survey of hemapheresis practice in Turkey (1998) q b Osman Ilhan a,*, Necdet Uskent , Onder Arslan a, Mutlu Arat a, f urk d, Sevgi B. Kalayo Fahir Ozkalemkas uly uz Ozt glu e, Ahmet Ozet , ß c, G Murat Tombulo glu g, Fikret Arpacõ f, Erc ument Ovalõ h, Sema Anak i a
Department of Hematology, Ankara University Medical School, Hemapheresis Unit, Sihhiye 06100, Ankara, Turkey b Department of Hematology±Oncology, Haydarpasßa G ulhane Military Medical School, Turkey c Department of Hematology, Uluda g University Medical School, Turkey d Department of Pediatric Hematology, Gazi University Medical School, Turkey e Department of Hematology, Istanbul University Medical School, Turkey f Department of Oncology, Ankara G ulhane Military Medical School, Turkey g Department of Hematology, Ege University Medical School, Turkey h Department of Hematology, Karadeniz Technical University Medical School, Turkey i Our Leukemic ChildrenÕs Foundation, Turkey
Abstract The Turkish Apheresis Group has maintained a national registry for apheresis activities since 1997. The hemapheresis practice of Turkey in 1998 is summarized in brief detail in this article. A total of 30,136 apheresis procedures were performed at 31 dierent apheresis centers. At 10 centers, 145 peripheral blood stem cell (PBSC) apheresis were performed on 82 patients in allogeneic setting and at 17 centers, 981 PBSC apheresis were performed on 271 patients in autologous setting. Frequently observed adverse eects during PBSC apheresis were mild tremor and chills, paresthesia and nausea in 15% of the patients and donors. Vascular access complications, particularly observed in autologous setting due to central venous catheters were encountered in 10% of the procedures. Eight hundred and sixty-nine therapeutic plasma exchange procedures were performed at 21 centers on 172 patients, most commonly for neurological disorders and thrombotic thrombocytopenic purpura (TTP)/hemolyic uremic syndrome (HUS). Therapeutic cytapheresis procedures like leukapheresis, plateletapheresis and erythrocyte apheresis were performed especially for cytoreduction in myeloproliferative disorders. A total of 204 cytapheresis procedures (66% leukapheresis, 33% plateletapheresis and 1% erythrocytapheresis) were performed on 134 patients in 15 centers. Donor plateletapheresis was the most used apheresis procedure, reaching a total of 28.016 in 1998. Many university hospitals and a few state hospitals are performing above-mentioned apheresis procedures with great success and acceptable side eects. According to these data we are planning prospective trials and will establish National Standards of Practice. Ó 2000 Published by Elsevier Science Ltd. All rights reserved.
q
The authors represent the Turkish Apheresis group (TAG). Corresponding author. Tel.: +90-312-310333; fax: +90-3123115474. E-mail address: [email protected] (O. Ilhan). *
0955-3886/00/$ - see front matter Ó 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 5 - 3 8 8 6 ( 0 0 ) 0 0 0 5 7 - 6
196
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
Participating centers (members of Turkish Apheresis Group ± TAG 1) Akdeniz University Medical School Department of Hematology Ankara G ulhane Military Medical School Department of Hematology Ankara G ulhane Military Medical School Department of Oncology Ankara Numune Hospital Blood Bank and Apheresis Unit Ankara Oncology Hospital Blood Bank and Apheresis Unit Ankara University Medical School Department of Hematology and Apheresis Unit Basßkent University Blood Bank and Apheresis Unit Our Leukemic ChildrenÕs Foundation Istanbul University Cerrahpasßa Medical School Department of Hematology C ß ukurova University Medical School Department of Hematology-Oncology C ß ukurova University Medical School Department of Pediatric Hematology C ß ukurova University Medical School Blood Bank and Apheresis Unit Ege University Medical School Department of Hematology Erciyes University Medical School Department of Hematology-Oncology Gazi University Medical School Department of Pediatric Hematology Hacettepe University Medical School Department of Pediatric Hematology Hacettepe University Medical School Department of Hematology Hacettepe University Medical School Department of Oncology Haydarpasßa G ulhane Military Medical School Department of Hematology-Oncology Haydarpasßa Numune Hospital Blood Bank and Apheresis Unit In on u University Medical School Department of Hematology Istanbul University Medical School Department of Hematology Istanbul University Medical School Department of Pediatric Hematology Karadeniz Technical University Medical School Department of Hematology Marmara University Medical School Department of Hematology Nazilli State Hospital On Dokuz Mayõs University Medical School Department of Hematology Osman Gazi University Medical School Department of Hematology
1
in alphabetical order.
Trakya University Medical School Department of Hematology Uluda g University Medical School Department of Hematology Y uz unc u Yõl University Medical School Department of Hematology
1. Allogeneic PBSC apheresis 1.1. Introduction The rate of utilizing peripheral blood stem cells as a source for allogeneic stem cell transplantation is growing gradually. The ®rst allogeneic PBSC apheresis in Turkey was performed in 1993 and afterwards many centers adapted this method for stem cell collection both in allogeneic and autologous settings. Our subcommittee sent a uniform questionnaire asking about the details of apheresis procedures, current status of the patient and indication. 1.2. Patients and methods At 10 centers 145 stem cell collection procedures were performed on 82 HLA identical healthy sibling donors (M/F:55/27) using three dierent continuous ¯ow cell separators (Baxter Fenwall CS3000+, Cobe Spectra, Fresenius AS204). The characteristics of healthy donors are summarized in Table 1. Major indications for allogeneic PBSC collection were AML:45 (55%), CML:18 (21%) and ALL:8 (10%) (Table 2). DonorsÕ median age was 28 years. Nine procedures were performed for pediatric recipients. Table 1 Characteristics of healthy donors Mean Age (median) Gender (F/M) Body weight (kg) Total blood volume (ml) Preapheresis Hb (g/l) WBC (109 /l) Preapheresis PLT. (109 /l)
28.2 36/46 70.3 4935 144 39.9 228,4
Minimum
Maximum
5
59
22 1720
105 7350
96 5.7 117
165 67.9 480
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201 Table 2 Diagnosis of the patients
Table 4 Characteristics of harvest material
Diagnosis
Patient number
AML CML ALL MDS Aplastic anemia Solid tumors SCID
45 18 8 5 4 1 1
Total
82
Harvest volume (ml) Harvest nucleated cells (108 /kg) Harvest mono nuclear cells (108 /kg) Harvest CD34 cells (106 /kg)
1.3. Results Donors mainly received rhG-CSF (Neupogen, Amgen, ROCHE) 5±10 lg=kg=day sc. for 4±5 days. As a target value 4 106 =kg (per recipient body weight) CD34 cells is widely accepted among BMT Units and Apheresis Centers. This target was reached in 54% of donors at the ®rst cycle, 38% at the second cycle, and for the remaining with further cycles. We noticed that these poor mobilizers were especially the donors who received lower doses of growth factors. In all patients, peripheral veins were used for venous access. None of the donors necessitated an insertion of central venous catheter. Apheresis procedure data and product characteristics are shown in the Table 3. Apheresis characteristics are summarized in Table 4. Side eects, most frequently encountered were ¯u-like syndrome and bone pain due to rhGCSF. 1.4. Conclusion Collection of peripheral blood stem cells in allogeneic setting with continuous ¯ow cell separators is well tolerated and the harvest material contains very high values of CD34 cells. As the Table 3 Characteristics of apheresis procedures Volume processed (ml) Duration (min) ACD (ml)
197
Mean
Minimum
Maximum
14,245
3054
17,100
203 950
100 260
310 1155
Mean
Minimum
Maximum
253 10.6
55 1.48
352 24.5
6.8
1.3
9.1
6.7
2.18
7.4
debate about the use of rhG-CSF in healthy donors is disappearing, we share the opinion that the use of peripheral blood progenitor cells as stem cell source will be widely accepted especially in the setting of positive and negative selections and adoptive immunotherapies. 2. Autologous PBSC apheresis High-dose chemotherapy (HDC) with autologous stem cell support is widely used especially for acute leukemia, lymphoma, multiple myeloma and in recent years for solid tumors like (germ cell tumors, ovarian carcinoma, breast cancer etc.). The ®rst successful autologous peripheral blood stem cell (autoPBSC) apheresis in Turkey was performed in 1992 and the number of apheresis and transplantation centers using this therapy approach is rapidly growing every year. In 1998 according to EBMT data, the majority of transplant centers (93%) used PBSC as stem cell source in autologous stem cell transplantation. In the same period according to our national survey 955 autoPBSC apheresis procedures were performed at 17 centers on 271 patients. 2.1. Patients and methods Median age of the patients was 34.5 (8±57) years with a male/female ratio of 160/111. Thirtyone (11%) of the patients were in pediatric age group. PatientsÕ diagnoses are given in detail in Table 5. Mobilization protocols consisted of hematopoietic growth factors alone in 19% of patients and chemotherapy plus growth factors in 81%. The
198
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
median number of days after mobilization regimen to start collection was 10 (5±17) days. All the procedures were performed by using continuous ¯ow cell separators. There is no established standards for the on-set of collection. While many centers are using the day of MNC>1.5±5109 =l, a few centers start leukapheresis according to absolute peripheral blood CD34 counts. Median no. of collection procedures for all patients were 3 (1±8). Large volume leukapheresis was performed on 11 (4%) patients. Two or three times the total blood volume was processed in each cycle of the patients. A median of 6.1 0:3±12:4 108 =kg MNC and 4:3 0:4±25:7 106 =kg CD34 cells were collected (Table 6). 2.2. Conclusion AutoPBSC apheresis is a well-established procedure in Turkey not only in adult but also in pediatric patients. This technique enables not only the collection of sucient stem cells easily but also processing for positive and negative selection to reduce the tumor cell contamination. A national database should be established to standardize the procedures and to have feasible and reliable data collection. Table 5 Diagnosis of the patients Diagnosis
n
Acute non-lymphoblastic Leukemia Non-HodgkinÕs lymphoma Solid tumors HodgkinÕs disease Multiple myeloma Other haematological malignancies Total
%
60 58 57 44 38 14
22 22 21 16 14 5
271
100
(1) (2) (3) (4)
No intervention required Intervention required, the procedure may be interrupted but is completed The procedure has to be terminated because of the severity of the symptoms The patient has expired during the procedure
3. PBSC apheresis complications 3.1. Introduction PBSC apheresis both in autologous and allogeneic setting is currently performed at 15 apheresis units in practice. In order to assess the immediate side eects during each apheresis procedure with currently used instruments, our subcommittee conducted a survey in 1998 using a uniform questionnaire. Fifteen centers responded to our survey and, 525 PBSC apheresis cycles in total were evaluated. In this questionnaire, complications were divided into 3 dierent areas; vascular access, symptoms and ®ndings, and technical problems. Fifteen apheresis centers reported 143 events in 525 procedures (115 allogeneic, 22% and 410 autologous, 78%). Complications were graded in 0±IV scale according to their eect on the completion of apheresis procedure (Table 7). 3.2. Patients and methods For venous access, peripheral veins were used in all allogeneic PBSC apheresis. In autologous setting 178 non-permanent central venous catheters (CVC) (85% subclavian, 11% internal jugular and 4% femoral) and 30 semi-implantable catheters Table 8 Characteristics of the central venous catheters used for apheresis
Table 6 Characteristics of the harvest Harvest mono nuclear cells (108 /kg) Harvest CD34 cells (106 /kg)
Table 7 Grading scale of the complications
Mean
Minimum
Maximum
6.1
0.3
12.4
4.3
0.4
25.7
Non-permanent CVC (n 178) (%)
Semi-implantable (tunnelled) CVC (n 30) (%)
Subclavian Internal jugular Femoral
Hickman-like Apheresis Catheters (Hemodialysis)
85 11 4
70 30
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
199
Table 9 General summary of the apheresis complications reported N (%)
Symptoms and signs (%)
Vascular access problems (%)
Technical problems (%)
Allogeneic Autologous
115 (22) 410 (78)
18 (22) 64 (78)
7 (13) 46 (87)
1 (13) 8 (87)
Total
525 (26.5)
82 (15)
53 (10)
8 (1.5)
(70% Hickman like and 30% tunneled apheresis catheters) were used for PBSC apheresis (Table 8). All apheresis procedures were performed with continuous ¯ow cell separators. 3.3. Results Total number of the complications and their distribution are summarized in Table 9. Eighty-two events (18 allo and 64 auto) were attributed to symptoms and signs of the patients (donors). Main side eects encountered were tremor and shivering (39%), mild paresthesia (20%), nausea (20%) and hypotension (9%) which were in Grade I and II (Tables 10 and 11). Vascular access complications (53 events; 7 allo and 46 auto) mostly reported were occlusion (73%), low input sign (18%) and hematoma formation (6%). Grade III complications were reported only for catheter occlusions, on which apheresis procedures were prematurely terminated (Table 12). Most of the technical problems were due to disposable sets and after replacement the procedures were successfully completed.
Shivering Paresthesia Nausea Hypotension Urticaria Abdominal pain Vertigo Flushing Total
n (Grade) 42 (I±II) 22 (I±II) 21 (I±II) 10 (I±II) 4 (I±II) 4 (I±II) 3 (I) 2 (I) 108
Allogeneic Autologous
Grade I
Grade II
Grade III
Total
15 50
3 14
0 1
18 64
Table 12 Vascular access complications Type
N (Grade)
Occlusion Other (low input) Hematoma formation Post-procedural bleeding Catheter infection
22 (I±III) 4 (I±II) 2 (I±II) 1 (I±II) 1 (I±II)
Total
30
% 73 18 6 2 1 100
3.4. Conclusion In Turkey PBSC apheresis procedures are relatively safe, with a 13.7% overall incidence, most commonly with reversible side eects. TAG is planning an on-line adverse eect submission form in the future for further analysis. 4. Therapeutic plasma exchange
Table 10 Symptoms and signs during leukapheresis Symptoms and signs
Table 11 Frequency of symptoms and signs according to their grade
% 39 20 20 9 4 4 2 2 100
In 1998 therapeutic plasma exchange (TPE) was performed in 21 centers. Total number of patients were 172 and total TPE cycles were 869. Major indications for plasma exchange were thrombotic thrombocytopenic purpura (TTP) and hemolyic uremic syndrome (HUS) (Figs. 1 and 2). Patient characteristics and data about the TPE procedure are summarized in Table 13. In most of the procedures one plasma volume was changed but there were few patients with lower plasma volume
200
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201 Table 14 Distribution of replacement ¯uids used Fresh frozen plasma Human albumin 6% HES
50% 40% 10%
Table 15 Comparison of plasmapheresis activity in dierent countries [1]
Fig. 1. Diagnosis of patients who underwent TPE: TTP ± Thrombotic thrombocytopenic purpura; MG ± Myasthenia Gravis; GBS ± Gullian Barre Syndrome; MS ± Multiple Sclerosis; Post-Tx ± Post-allogeneic stem cell transplantation developed aregeneratoric anemia due to major blood group mismatch; ITP ± Idiopathic thrombocytopenic purpura; GPS ± Good Pasture Syndrome.
Canada (CAG) France (FAG) Sweden (SAG) Turkey (TAG)
Number of patients
Number of apheresis
TPE per person
720 898 439 172
8392 8100 3562 869
2.4 ´ 10ÿ4 1.3 ´ 10ÿ4 3.5 ´ 10ÿ4 1.3 ´ 10ÿ5
quently used replacement ¯uid in our survey (Table 14). 4.1. Results The results of our survey revealed that except multiple sclerosis and ITP all the indications for TPE were in Group I or II of American Association of Blood Banks (AABB) and American Society for Apheresis (ASFA) criteria. In our country TPE per inhabitant was calculated as 1:3 10ÿ5 . The comparison of TPE activity with other developed countries is demonstrated in Table 15. 4.2. Conclusion
Fig. 2. Main indications for TPE in Turkey. Table 13 Characteristics of the patients and procedures N Gender M/F Age Volume replaced Median number of procedures
172 99/73 38 (14±68) 0.5±1.5 PV) 4 (1±75)
exchanged due to cardiovascular status and the decision of the apheresis team. Currently according to the indication of the plasmapheresis procedure isoosmotic replacement ¯uids like fresh frozen plasma, 5% human albumin, pentastarch and cryosupernatant are mainly in use. Fresh frozen plasma was the most fre-
Though plasmapheresis activity per inhabitant is lower than many developed countries, our yearly activity is progressing. There is an urgent need for a national central database system for collection of update plasmapheresis data more comprehensive and ecient. In order to increase the number of TPE procedures, we are planning to collaborate with nephrology, neurology and immunology. 5. Therapeutic cytapheresis In 1998, 204 therapeutic cytapheresis (TC) procedures were performed on 204 patients at 18 apheresis centers. Therapeutic leukapheresis was performed in 15 centers for 81 patients. A total of 136 leukapher-
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
esis procedures, mainly for cytoreduction, were performed for patients with diagnosis of AML (44%), CML (44%), ALL (8%) and CLL (3%). All procedures resulted with successful reduction of white blood cells. Therapeutic plateletapheresis was performed in 7 centers for 50 patients. A total of 63 plateletapheresis procedures, mainly for cytoreduction, were perfomed for patients mainly with diagnosis of CML (48%) and ET (36%). All the procedures resulted with successful reduction of platelets. Therapeutic erythrocytapheresis was performed in 3 centers on 5 patients for sickle cell anemia.
201
6. Donor plateletapheresis Donor plateletapheresis was the mostly used apheresis procedure in more than 30 centers reaching a total number of 28.016 in 1998.
References [1] Post-graduate Course: Therapeutic Hemapheresis for clinical specialists using hemo-immuno-therapy, Malm o, Sweden, 10±11 September 1999.
www.elsevier.com/locate/transci
National survey of hemapheresis practice in Turkey (1998) q b Osman Ilhan a,*, Necdet Uskent , Onder Arslan a, Mutlu Arat a, f urk d, Sevgi B. Kalayo Fahir Ozkalemkas uly uz Ozt glu e, Ahmet Ozet , ß c, G Murat Tombulo glu g, Fikret Arpacõ f, Erc ument Ovalõ h, Sema Anak i a
Department of Hematology, Ankara University Medical School, Hemapheresis Unit, Sihhiye 06100, Ankara, Turkey b Department of Hematology±Oncology, Haydarpasßa G ulhane Military Medical School, Turkey c Department of Hematology, Uluda g University Medical School, Turkey d Department of Pediatric Hematology, Gazi University Medical School, Turkey e Department of Hematology, Istanbul University Medical School, Turkey f Department of Oncology, Ankara G ulhane Military Medical School, Turkey g Department of Hematology, Ege University Medical School, Turkey h Department of Hematology, Karadeniz Technical University Medical School, Turkey i Our Leukemic ChildrenÕs Foundation, Turkey
Abstract The Turkish Apheresis Group has maintained a national registry for apheresis activities since 1997. The hemapheresis practice of Turkey in 1998 is summarized in brief detail in this article. A total of 30,136 apheresis procedures were performed at 31 dierent apheresis centers. At 10 centers, 145 peripheral blood stem cell (PBSC) apheresis were performed on 82 patients in allogeneic setting and at 17 centers, 981 PBSC apheresis were performed on 271 patients in autologous setting. Frequently observed adverse eects during PBSC apheresis were mild tremor and chills, paresthesia and nausea in 15% of the patients and donors. Vascular access complications, particularly observed in autologous setting due to central venous catheters were encountered in 10% of the procedures. Eight hundred and sixty-nine therapeutic plasma exchange procedures were performed at 21 centers on 172 patients, most commonly for neurological disorders and thrombotic thrombocytopenic purpura (TTP)/hemolyic uremic syndrome (HUS). Therapeutic cytapheresis procedures like leukapheresis, plateletapheresis and erythrocyte apheresis were performed especially for cytoreduction in myeloproliferative disorders. A total of 204 cytapheresis procedures (66% leukapheresis, 33% plateletapheresis and 1% erythrocytapheresis) were performed on 134 patients in 15 centers. Donor plateletapheresis was the most used apheresis procedure, reaching a total of 28.016 in 1998. Many university hospitals and a few state hospitals are performing above-mentioned apheresis procedures with great success and acceptable side eects. According to these data we are planning prospective trials and will establish National Standards of Practice. Ó 2000 Published by Elsevier Science Ltd. All rights reserved.
q
The authors represent the Turkish Apheresis group (TAG). Corresponding author. Tel.: +90-312-310333; fax: +90-3123115474. E-mail address: [email protected] (O. Ilhan). *
0955-3886/00/$ - see front matter Ó 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 5 - 3 8 8 6 ( 0 0 ) 0 0 0 5 7 - 6
196
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
Participating centers (members of Turkish Apheresis Group ± TAG 1) Akdeniz University Medical School Department of Hematology Ankara G ulhane Military Medical School Department of Hematology Ankara G ulhane Military Medical School Department of Oncology Ankara Numune Hospital Blood Bank and Apheresis Unit Ankara Oncology Hospital Blood Bank and Apheresis Unit Ankara University Medical School Department of Hematology and Apheresis Unit Basßkent University Blood Bank and Apheresis Unit Our Leukemic ChildrenÕs Foundation Istanbul University Cerrahpasßa Medical School Department of Hematology C ß ukurova University Medical School Department of Hematology-Oncology C ß ukurova University Medical School Department of Pediatric Hematology C ß ukurova University Medical School Blood Bank and Apheresis Unit Ege University Medical School Department of Hematology Erciyes University Medical School Department of Hematology-Oncology Gazi University Medical School Department of Pediatric Hematology Hacettepe University Medical School Department of Pediatric Hematology Hacettepe University Medical School Department of Hematology Hacettepe University Medical School Department of Oncology Haydarpasßa G ulhane Military Medical School Department of Hematology-Oncology Haydarpasßa Numune Hospital Blood Bank and Apheresis Unit In on u University Medical School Department of Hematology Istanbul University Medical School Department of Hematology Istanbul University Medical School Department of Pediatric Hematology Karadeniz Technical University Medical School Department of Hematology Marmara University Medical School Department of Hematology Nazilli State Hospital On Dokuz Mayõs University Medical School Department of Hematology Osman Gazi University Medical School Department of Hematology
1
in alphabetical order.
Trakya University Medical School Department of Hematology Uluda g University Medical School Department of Hematology Y uz unc u Yõl University Medical School Department of Hematology
1. Allogeneic PBSC apheresis 1.1. Introduction The rate of utilizing peripheral blood stem cells as a source for allogeneic stem cell transplantation is growing gradually. The ®rst allogeneic PBSC apheresis in Turkey was performed in 1993 and afterwards many centers adapted this method for stem cell collection both in allogeneic and autologous settings. Our subcommittee sent a uniform questionnaire asking about the details of apheresis procedures, current status of the patient and indication. 1.2. Patients and methods At 10 centers 145 stem cell collection procedures were performed on 82 HLA identical healthy sibling donors (M/F:55/27) using three dierent continuous ¯ow cell separators (Baxter Fenwall CS3000+, Cobe Spectra, Fresenius AS204). The characteristics of healthy donors are summarized in Table 1. Major indications for allogeneic PBSC collection were AML:45 (55%), CML:18 (21%) and ALL:8 (10%) (Table 2). DonorsÕ median age was 28 years. Nine procedures were performed for pediatric recipients. Table 1 Characteristics of healthy donors Mean Age (median) Gender (F/M) Body weight (kg) Total blood volume (ml) Preapheresis Hb (g/l) WBC (109 /l) Preapheresis PLT. (109 /l)
28.2 36/46 70.3 4935 144 39.9 228,4
Minimum
Maximum
5
59
22 1720
105 7350
96 5.7 117
165 67.9 480
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201 Table 2 Diagnosis of the patients
Table 4 Characteristics of harvest material
Diagnosis
Patient number
AML CML ALL MDS Aplastic anemia Solid tumors SCID
45 18 8 5 4 1 1
Total
82
Harvest volume (ml) Harvest nucleated cells (108 /kg) Harvest mono nuclear cells (108 /kg) Harvest CD34 cells (106 /kg)
1.3. Results Donors mainly received rhG-CSF (Neupogen, Amgen, ROCHE) 5±10 lg=kg=day sc. for 4±5 days. As a target value 4 106 =kg (per recipient body weight) CD34 cells is widely accepted among BMT Units and Apheresis Centers. This target was reached in 54% of donors at the ®rst cycle, 38% at the second cycle, and for the remaining with further cycles. We noticed that these poor mobilizers were especially the donors who received lower doses of growth factors. In all patients, peripheral veins were used for venous access. None of the donors necessitated an insertion of central venous catheter. Apheresis procedure data and product characteristics are shown in the Table 3. Apheresis characteristics are summarized in Table 4. Side eects, most frequently encountered were ¯u-like syndrome and bone pain due to rhGCSF. 1.4. Conclusion Collection of peripheral blood stem cells in allogeneic setting with continuous ¯ow cell separators is well tolerated and the harvest material contains very high values of CD34 cells. As the Table 3 Characteristics of apheresis procedures Volume processed (ml) Duration (min) ACD (ml)
197
Mean
Minimum
Maximum
14,245
3054
17,100
203 950
100 260
310 1155
Mean
Minimum
Maximum
253 10.6
55 1.48
352 24.5
6.8
1.3
9.1
6.7
2.18
7.4
debate about the use of rhG-CSF in healthy donors is disappearing, we share the opinion that the use of peripheral blood progenitor cells as stem cell source will be widely accepted especially in the setting of positive and negative selections and adoptive immunotherapies. 2. Autologous PBSC apheresis High-dose chemotherapy (HDC) with autologous stem cell support is widely used especially for acute leukemia, lymphoma, multiple myeloma and in recent years for solid tumors like (germ cell tumors, ovarian carcinoma, breast cancer etc.). The ®rst successful autologous peripheral blood stem cell (autoPBSC) apheresis in Turkey was performed in 1992 and the number of apheresis and transplantation centers using this therapy approach is rapidly growing every year. In 1998 according to EBMT data, the majority of transplant centers (93%) used PBSC as stem cell source in autologous stem cell transplantation. In the same period according to our national survey 955 autoPBSC apheresis procedures were performed at 17 centers on 271 patients. 2.1. Patients and methods Median age of the patients was 34.5 (8±57) years with a male/female ratio of 160/111. Thirtyone (11%) of the patients were in pediatric age group. PatientsÕ diagnoses are given in detail in Table 5. Mobilization protocols consisted of hematopoietic growth factors alone in 19% of patients and chemotherapy plus growth factors in 81%. The
198
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
median number of days after mobilization regimen to start collection was 10 (5±17) days. All the procedures were performed by using continuous ¯ow cell separators. There is no established standards for the on-set of collection. While many centers are using the day of MNC>1.5±5109 =l, a few centers start leukapheresis according to absolute peripheral blood CD34 counts. Median no. of collection procedures for all patients were 3 (1±8). Large volume leukapheresis was performed on 11 (4%) patients. Two or three times the total blood volume was processed in each cycle of the patients. A median of 6.1 0:3±12:4 108 =kg MNC and 4:3 0:4±25:7 106 =kg CD34 cells were collected (Table 6). 2.2. Conclusion AutoPBSC apheresis is a well-established procedure in Turkey not only in adult but also in pediatric patients. This technique enables not only the collection of sucient stem cells easily but also processing for positive and negative selection to reduce the tumor cell contamination. A national database should be established to standardize the procedures and to have feasible and reliable data collection. Table 5 Diagnosis of the patients Diagnosis
n
Acute non-lymphoblastic Leukemia Non-HodgkinÕs lymphoma Solid tumors HodgkinÕs disease Multiple myeloma Other haematological malignancies Total
%
60 58 57 44 38 14
22 22 21 16 14 5
271
100
(1) (2) (3) (4)
No intervention required Intervention required, the procedure may be interrupted but is completed The procedure has to be terminated because of the severity of the symptoms The patient has expired during the procedure
3. PBSC apheresis complications 3.1. Introduction PBSC apheresis both in autologous and allogeneic setting is currently performed at 15 apheresis units in practice. In order to assess the immediate side eects during each apheresis procedure with currently used instruments, our subcommittee conducted a survey in 1998 using a uniform questionnaire. Fifteen centers responded to our survey and, 525 PBSC apheresis cycles in total were evaluated. In this questionnaire, complications were divided into 3 dierent areas; vascular access, symptoms and ®ndings, and technical problems. Fifteen apheresis centers reported 143 events in 525 procedures (115 allogeneic, 22% and 410 autologous, 78%). Complications were graded in 0±IV scale according to their eect on the completion of apheresis procedure (Table 7). 3.2. Patients and methods For venous access, peripheral veins were used in all allogeneic PBSC apheresis. In autologous setting 178 non-permanent central venous catheters (CVC) (85% subclavian, 11% internal jugular and 4% femoral) and 30 semi-implantable catheters Table 8 Characteristics of the central venous catheters used for apheresis
Table 6 Characteristics of the harvest Harvest mono nuclear cells (108 /kg) Harvest CD34 cells (106 /kg)
Table 7 Grading scale of the complications
Mean
Minimum
Maximum
6.1
0.3
12.4
4.3
0.4
25.7
Non-permanent CVC (n 178) (%)
Semi-implantable (tunnelled) CVC (n 30) (%)
Subclavian Internal jugular Femoral
Hickman-like Apheresis Catheters (Hemodialysis)
85 11 4
70 30
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
199
Table 9 General summary of the apheresis complications reported N (%)
Symptoms and signs (%)
Vascular access problems (%)
Technical problems (%)
Allogeneic Autologous
115 (22) 410 (78)
18 (22) 64 (78)
7 (13) 46 (87)
1 (13) 8 (87)
Total
525 (26.5)
82 (15)
53 (10)
8 (1.5)
(70% Hickman like and 30% tunneled apheresis catheters) were used for PBSC apheresis (Table 8). All apheresis procedures were performed with continuous ¯ow cell separators. 3.3. Results Total number of the complications and their distribution are summarized in Table 9. Eighty-two events (18 allo and 64 auto) were attributed to symptoms and signs of the patients (donors). Main side eects encountered were tremor and shivering (39%), mild paresthesia (20%), nausea (20%) and hypotension (9%) which were in Grade I and II (Tables 10 and 11). Vascular access complications (53 events; 7 allo and 46 auto) mostly reported were occlusion (73%), low input sign (18%) and hematoma formation (6%). Grade III complications were reported only for catheter occlusions, on which apheresis procedures were prematurely terminated (Table 12). Most of the technical problems were due to disposable sets and after replacement the procedures were successfully completed.
Shivering Paresthesia Nausea Hypotension Urticaria Abdominal pain Vertigo Flushing Total
n (Grade) 42 (I±II) 22 (I±II) 21 (I±II) 10 (I±II) 4 (I±II) 4 (I±II) 3 (I) 2 (I) 108
Allogeneic Autologous
Grade I
Grade II
Grade III
Total
15 50
3 14
0 1
18 64
Table 12 Vascular access complications Type
N (Grade)
Occlusion Other (low input) Hematoma formation Post-procedural bleeding Catheter infection
22 (I±III) 4 (I±II) 2 (I±II) 1 (I±II) 1 (I±II)
Total
30
% 73 18 6 2 1 100
3.4. Conclusion In Turkey PBSC apheresis procedures are relatively safe, with a 13.7% overall incidence, most commonly with reversible side eects. TAG is planning an on-line adverse eect submission form in the future for further analysis. 4. Therapeutic plasma exchange
Table 10 Symptoms and signs during leukapheresis Symptoms and signs
Table 11 Frequency of symptoms and signs according to their grade
% 39 20 20 9 4 4 2 2 100
In 1998 therapeutic plasma exchange (TPE) was performed in 21 centers. Total number of patients were 172 and total TPE cycles were 869. Major indications for plasma exchange were thrombotic thrombocytopenic purpura (TTP) and hemolyic uremic syndrome (HUS) (Figs. 1 and 2). Patient characteristics and data about the TPE procedure are summarized in Table 13. In most of the procedures one plasma volume was changed but there were few patients with lower plasma volume
200
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201 Table 14 Distribution of replacement ¯uids used Fresh frozen plasma Human albumin 6% HES
50% 40% 10%
Table 15 Comparison of plasmapheresis activity in dierent countries [1]
Fig. 1. Diagnosis of patients who underwent TPE: TTP ± Thrombotic thrombocytopenic purpura; MG ± Myasthenia Gravis; GBS ± Gullian Barre Syndrome; MS ± Multiple Sclerosis; Post-Tx ± Post-allogeneic stem cell transplantation developed aregeneratoric anemia due to major blood group mismatch; ITP ± Idiopathic thrombocytopenic purpura; GPS ± Good Pasture Syndrome.
Canada (CAG) France (FAG) Sweden (SAG) Turkey (TAG)
Number of patients
Number of apheresis
TPE per person
720 898 439 172
8392 8100 3562 869
2.4 ´ 10ÿ4 1.3 ´ 10ÿ4 3.5 ´ 10ÿ4 1.3 ´ 10ÿ5
quently used replacement ¯uid in our survey (Table 14). 4.1. Results The results of our survey revealed that except multiple sclerosis and ITP all the indications for TPE were in Group I or II of American Association of Blood Banks (AABB) and American Society for Apheresis (ASFA) criteria. In our country TPE per inhabitant was calculated as 1:3 10ÿ5 . The comparison of TPE activity with other developed countries is demonstrated in Table 15. 4.2. Conclusion
Fig. 2. Main indications for TPE in Turkey. Table 13 Characteristics of the patients and procedures N Gender M/F Age Volume replaced Median number of procedures
172 99/73 38 (14±68) 0.5±1.5 PV) 4 (1±75)
exchanged due to cardiovascular status and the decision of the apheresis team. Currently according to the indication of the plasmapheresis procedure isoosmotic replacement ¯uids like fresh frozen plasma, 5% human albumin, pentastarch and cryosupernatant are mainly in use. Fresh frozen plasma was the most fre-
Though plasmapheresis activity per inhabitant is lower than many developed countries, our yearly activity is progressing. There is an urgent need for a national central database system for collection of update plasmapheresis data more comprehensive and ecient. In order to increase the number of TPE procedures, we are planning to collaborate with nephrology, neurology and immunology. 5. Therapeutic cytapheresis In 1998, 204 therapeutic cytapheresis (TC) procedures were performed on 204 patients at 18 apheresis centers. Therapeutic leukapheresis was performed in 15 centers for 81 patients. A total of 136 leukapher-
O. Ilhan et al. / Transfusion Science 22 (2000) 195±201
esis procedures, mainly for cytoreduction, were performed for patients with diagnosis of AML (44%), CML (44%), ALL (8%) and CLL (3%). All procedures resulted with successful reduction of white blood cells. Therapeutic plateletapheresis was performed in 7 centers for 50 patients. A total of 63 plateletapheresis procedures, mainly for cytoreduction, were perfomed for patients mainly with diagnosis of CML (48%) and ET (36%). All the procedures resulted with successful reduction of platelets. Therapeutic erythrocytapheresis was performed in 3 centers on 5 patients for sickle cell anemia.
201
6. Donor plateletapheresis Donor plateletapheresis was the mostly used apheresis procedure in more than 30 centers reaching a total number of 28.016 in 1998.
References [1] Post-graduate Course: Therapeutic Hemapheresis for clinical specialists using hemo-immuno-therapy, Malm o, Sweden, 10±11 September 1999.