Granulozytensupport in der Therapie der akuten Leukämie, eine Chance?

Transcription

1 Granulozytensupport in der Therapie der akuten Leukämie, eine Chance? Volker Witt in cooperation with TFM MUW Vienna

2 Anti-infective prophylaxis in pediatric patients with acute myeloid leukemia. Lehrnbecher T 1, Sung L. Expert Rev Hematol Dec;7(6): doi: / Epub 2014 Oct 31. Abstract Pediatric patients undergoing treatment for acute myeloid leukemia (AML) are at high risk for infectious complications, predominantly due to Gram-negative bacteria, viridans group streptococci and fungal pathogens. In order to prevent infections in these patients, most institutions have implemented a number of non-pharmacological approaches to supportive care. In addition, antibiotic prophylaxis reduces bacterial infection, but may increase the emergence of resistance. Antifungal prophylaxis is generally recommended for children with AML. Whereas the use of hematopoietic growth factors has not resulted in improved survival, the efficacy of prophylactic granulocyte transfusions has to be determined.

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4 The way of a Granulocyte concentrate day h before GCSF Dexa day 2 Ery- Plasmadepletion 30 Gy

5 How does it work collecting Granuloycyte concentrates plus HAES 6% to spread the lyers of platelets, Lymphocytes, Monocytes and Granulocytes => absolute necessary

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7 Who donates GT Volunteer donors Unrelated donors Mobilization with dexamethason 4 8 mg p.o. 8 h before donation Maximum 2 4 times a year due to the exposure to HAES 6% Family donors Related donors Mobilization with GCSF 5µg/kg 12 8 h before donation s.c. Maximum 5 times in one mobilization course due to the exposure to HAES 6% and GCSF

8 cell content of Granulocyte concentrates

9 Leitner G. Transfusion 2014

10 R.G. Strauss BJH 2012

11 R.G. Strauss BJH 2012

12 R.G. Strauss BJH 2012

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16 No maior surgery for pseudomonas leasons!!!

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19 Cinetic of Granulocyte transfusion

20 patient 1 10 / 12 girl Neuroblastom 4 diagnoses 04/1999 A-NB 94 protocoll 04/ /1999 Anti-GD2 3 cycles (01/ /2000) Local irradiation therapy 23,4 Gy 13-cis retinic acid 04/ /2000

21 Spezielle Anamnese/Klinik 2. HD-chemotherapy (Melphalan / VP16) d + 5 FUO in aplasia, CRP 0,4 mg/dl d + 6 CRP increase 13,8 mg/dl leason perianal + Vulva d + 7 increasing local leasons + Sepsis, CRP max. 27 mg/dl, suspected Pseudomonas Infektion, mobilization of the father d + 8 first GT CRP 20 mg/dl d + 9 guter AZ, Sepsis klinisch beherrscht, Läsionen rückläufig, CRP 9,8 mg/dl d + 14 Restitutio, CRP 0,3 mg/dl, Entlassung nach Hause

22 Granulocyte concentrate 1-2 x Granulozytes absolut 1.5 x 10 8 Granulozytes per kg KG Recommendation => 1 x Granulozyte per GT

23 GT from the father 100 ml product NC 407 x 10 3 /µl NC total 4.07 x Granulo 3.46 x MNC 0.61 x Mono 0.28 x Lympho 0.12 x Recipient 9.5 kg Cell count per kg KG NC total 0.43 x Granulo 0.36 x MNC x Mono x Lympho x 10 10

24 8,5 9,5 Granulozyten GK 5 4 Granulozyten Granuloxy Granuloxx

25 Granulocyte GK 5 4 Granulozyten Granuloxy Granuloxx

26 Granulocyte GK 5 4 Granulozyten Granuloxy Granuloxx ,5 9,

27 XY Granulocytes in peripheral blood of the reciepient 1,00E+11 Cell number of the GT 1,00E+10 1,00E+09 1,00E+08 Phase of main restitutio Elimination 1,00E+07 1,00E Detektionsgrenze => 2 Zellen/µl

28 MNC 1,8 1,6 1,4 GK 1,2 1 0,8 MNC MNCxy MNCxx 0,6 0,4 0, ,5 9 9,

29 MNC 1,8 1,6 1,4 GK 1,2 1 0,8 MNC MNCxy MNCxx 0,6 0,4 0, ,5 9 9,

30 MNC 1,8 1,6 1,4 GK 1,2 1 0,8 MNC MNCxy MNCxx 0,6 0,4 0, ,5 9 9,

31 XY. MNC in the peripheral blood of the recipient 1,00E+09 Cell count of the GT 1,00E+08 1,00E+07 Elimination 1,00E+06 Detektionsgrenze => 2 Zellen/µl

32 Last FISH d + 49 n Monozyten % XX Granulozyten % XX NK-Zellen % XX CD % XX CD % XX CD % XX

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35 Survey of all patients recieving Leukocytetransfusions from 2012 until 2014 Volker Witt

36 patients 24 patients treated at the St. Anna Kinderspital median age 9.47y (2.5 21y) sex 10 male; 11 female 255 GT in neutropenic life threatening infections

37 underlying disease

38 reason for neutropenia Leukemia 10 x SCTx 8 x chemotherapy Solid tumors 3 x chemotherapy Non malignant HLH => chemotherapy Agranulocytosis Septic Granulomatosis

39 Indication for GT Indication N= Pseudomonas Local +/- Sepsis 9 Local + Sepsis 4 SIRS 5 Aspergillom 3 Fusarium 1 Prophylactically 1

40 frequency of GT with side effects per patient N=15 without AE N=7 with AEs

41 adverse events after Granulocyte transfusion 7/24 patients with adverse events Patient # n/total GT 1 1/19 Fever 2 3/15 Fever Chills Dyspnoe 3 1/17 Fever Chills 4 1/26 Rash 5 1/6 Hypotension 6 3/20 Hypotension Fever Chills, Fever, tachcardia, resp. Insuff. 7 1/33 Chills Fever

42 Overal outcome

43 Outcome an indication

44 Outcome and pathogen

45 Outcome regarding to the condition of neutropenia

46 retrospective study, 10 year, single center cohort

47 conclusion There is still no randomized controlled trial in pediatric patients which shows clearly an advantage for GT in life threatening infections During the last 15 years empiric data suggest consistent the possible benefit of GT in life threatening infectious complications especially in local infections +/- Sepsis, but not in SIRS and MOF There are no consistent data about HLA, HNA, HPA before and after GT use in pediatric patients