www.ebmt.org #EBMT15

Invasive diagnostic procedures for infection complication in patient with

acute leukemia during chemotherapy induced pancytopenia and low

Karnofsky status.

Verona (Italy), October 29 - 30, 2015

Aleksander Shvetcov*,Marina Popova, Alisa Volkova, Anton Klimov, Stanislav Gorbunkov, Oleg Goloshapov, Olga Penegina, Ludmila Zubarovskaya,Oleg Galibin, Nikolai Klimko and Boris Afanasyev

Raisa Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of Saint-Petersburg, Saint-Petersburg, Russia (CIC 725)

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2

• Male 20 y

• Acute leukemia, mixed phenotype 46XY

• Normal chest CT scan before FLAG

Anamnesis

www.ebmt.org/events

DATE chemotherapy DATE effect donor

06/2013 RACOP-like 12/2013 No remission

12/2013 GMALL induction 03/2014 First remission, MRD(+) Donor search

(no sibling)

04/2014 GMALL consolidation 07/2014 First relapse (12 months)

07/2014 Re-induction GMALL 09/2014 No remission Donor found

09/2014 Admission at our clinic → FLAG scheduled day

of allo-HSCT

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3

14 day FLAG

neutropenic fever

→ cefoperazone sulbactam

16 day FLAG

still febrile

→ imipenem cilastatin

→ chest CT scan

→ BAL:

culture BAL Pseudomonas aeruginosa

galactomannan test in BAL – unknown

microscopy and culture - negative

Therapy modification:

+ polymyxin B

empiric Amphotericin B lipid complex 3 mg/kg

FLAG 2nd week

4

4

21 day FLAG

afebrile, no infection symptoms

ANC – 800

Bone marrow aspirate – no remission (50% blasts)

Still going to allo-HSCT (scheduled day 0 of alloHSCT MUD)

26 day FLAG

Fever and respiratory insufficiency grade 2-3

→ ICU, ventilation didn’t need

→ chest CT scan..

FLAG 3rd week

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5

FLAG 26 day

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6

FLAG 26 day

7

7

FLAG 27 day

→ BAL:

galactomannan test in BAL – unknown

microscopy – negative

culture – …

Pneumocystis jirovecii MONOFLUO test – positive

Therapy:

empiric Amphotericin B lipid complex

and

carbapenem with polymyxin B

trimethoprim-sulfamethoxazole was added

FLAG 4th week

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8

FLAG 28 day

→ no clinical improvement

→ highly suspected to IFD (mucormycosis ?)

Transthoracic ultrasonic guided biopsy

Hb 7.8 g/dl

ANC 900

PLT 25*109/l

Karnofsky

performance

status

40%

ECOG 3

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9

FLAG 28 day – On day of biopsy!

microscopy with calcofluor white :

septate hyphae branching at acute angles

Therapy modification:

stop amph B LC

start voriconazole + anidulafungin

Invasive mycosis (aspergillosis?) (proven, EORTC/MSG 2008)

Target antifungal therapy at the same day was started

Within one day of antifungal therapy a significant improvement in the general

condition was observed

Became afebrile in 24 hours

Diagnosis: Invasive Aspergillosis?

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10

31 day FLAG

3 days after biopsy

BAL and biopsy culture

Аspergillus ochraceus

Aspergillus fumigatus

Diagnosis: Invasive Aspergillosis

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11

FLAG 35 day

Antifungal therapy voriconazole

Start MAC: Bu Cy Ara-C CCNU + Cy Tacro MMF

MUD with mismatch loci A

D-0 31.10.2014

PBSC

6,5 CD34+/kg

Engraftment on D+27

Remission of AL

Full donor chimerizm

Complication of neutropenic phase

neutropenic fever (carbapenem with polymyxin B)

Allo-HSCT

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3 months therapy 6 months therapy

Result of therapy

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In 3 months after allo-HSCT

Stabilization (EORTC/MSG 2008) of IA

In 6 months after allo-HSCT

Partial (EORTC/MSG 2008) of IA

Switch antifungal therapy on posaconazole

In 9 months after allo-HSCT (clinical – no progression of IA, CT scan didn’t done)

Death from relapse of underling disease

Up to date

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There is no strong diagnostic algorithm with a place and time of lung

biopsy for infection complication in neutropenic patients

Conclusions 1

IFD, invasive fungal disease. *Further diagnosis could include bronchoscopy with bronchoalveloar lavage, microscopy using calcofluor or blancophor staining, galactomannan antigen, detection PCR and image‐guided or surgical biopsy of any lesions. †Multidisciplinary team input important at this stage.

(Adapted from Agrawal S, Hope W, Sinkó J, Kibbler C. Optimizing management of invasive mould diseases. J Antimicrob Chemother 2011;66 Suppl 1:i45−53. doi:10.1093/jac/dkq441).

Diagnostic‐driven antifungal therapy integrated care pathway

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BAL or Lung Biopsy

Chellapandian D, Lehrnbecher T et al,

Bronchoalveolar lavage and lung biopsy in patients with cancer and hematopoietic stem-cell transplantation recipients: a

systematic review and meta-analysis,

J Clin Oncol. 2015

BAL Lung Biopsy p value

BAL/BL

No. of studies/patients 72/4893 31/976

Infections disease 0,49

(0,45-0,54)

0,34

(0,28-0,42)

p<0,001

Non infections disease 0,07

(0,06-0,09)

0,43

(0,35-0,52)

p<0,001

Therapy correction 0,31 0,48 p=0,002

Complications 0,08 0,15 p=0,006

Postoperative mortality 0,0018 0,0078 p<0,001

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There is no strong diagnostic algorithm with a place and time of lung

biopsy for infection complication in neutropenic patients

Transthoracic ultrasonic guided biopsy is feasible invasive diagnostic

procedure for infection complication in patient with pancytopenia and

low Karnofsky status

Conclusions 2

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Informative – 89%

• aspergillosis - 5

• bacterial pneumonia – 4

• viral pneumonia – 3

• mucormycosis – 3

• tuberculosis - 1

• unknown - 2

Serious complication – 0%

Results of invasive diagnostic procedures

2008 – 2014 (18)

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19

There is no strong diagnostic algorithm with a place and time of lung

biopsy for infection complication in neutropenic patients

Transthoracic ultrasonic guided biopsy is feasible invasive diagnostic

procedures for infection complication in patient with pancytopenia and

low Karnofsky status

Invasive aspergillosis before the allo-HSCT did not impair the outcome

of the procedure with effective methods of diagnosis and prophylaxis

being used

Conclusions 3

20

20 Popova M. et al. Oral presentation at EBMT-2015 Istanbul, 23 mar 2015

factors p

duration of antifungal therapy before HSCT

<90 days vs ≥90 days

0,3

status of IA at the moment of HSCT

“active” IA vs PR vs CR

0,3

relapse/progression of IA after HSCT 0,2

65%, n=134, without IA before

allo-HSCT

57%, n=39, IA before allo-HSCT

Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Invasive Aspergillosis

Factors not associated with 1-year OS after allo-HSCT in patients with history of prior IA

Prospective observational singe-center study

173 pts / 195 allo-HSCT

[Dec 2012 – Jul 2013, median follow up 20 months]

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Acknowledgements:

All staff in R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation CIC 725

Dept. of Clinical Mycology, I. Mechnikov North-Western State Medical University, Saint-Petersburg

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Where is a place and time of lung biopsy for infection complication in

neutropenic patients?

What is the indication for invasive diagnostic (trigger for surgeon

consultation)?

Points for discussion