Emily Andersen, CNP AMG Hematology and Bone Marrow Transplant Objectives PTLD Incidence Risk factors Presentation Treatment/Chemotherapy Prognosis Anemia and Pancytopenia Risk.
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Transcript Emily Andersen, CNP AMG Hematology and Bone Marrow Transplant Objectives PTLD Incidence Risk factors Presentation Treatment/Chemotherapy Prognosis Anemia and Pancytopenia Risk.
Emily Andersen, CNP
AMG Hematology and Bone Marrow Transplant
Objectives
PTLD
Incidence
Risk factors
Presentation
Treatment/Chemotherapy
Prognosis
Anemia and Pancytopenia
Risk factors/types
Presentation
Treatment
Incidence
Who?
Patients exposed to systemic immunosuppression
EBV naïve at highest risk
More common in heart and lung transplants (10%)
Second most common malignancy in adult transplant
recipients; most common malignancy in pediatric
transplant recipients
What?
Expansion of recipient origin B cells latently infected
with EBV
May compromise graft function
Parker et al. (2010)
Incidence
Where?
HEENT most common, although it can occur anywhere
May even present in transplanted organ
When?
First year most common, but onset and duration are
variable amongst patients
Why?
“Impairment of EBV-specific, cytotoxic T-cell function
by systemic immunosuppression”
Largely EBV-driven – crosses from infection to
Parker et al. (2010)
malignancy
Smith (2010)
5-yr incidence of non-Hodgkin lymphoma
Relative risk of NHL:
Heart-lung
239.5
Lung
58.6
Heart
27.6
Liver
29.9
Pancreas
34.9
DD kidney Tx
12.6
Risk Factors
Transplant type
Small bowel > Lung > Heart/lung > Heart > Liver > Kidney
Immunosuppressive regimen
Cyclosporine vs Tacrolimus
Intensity of immunosuppression
Age
Under 10 and over 60 years of age
Parker et al. (2010)
Approximate Frequency of PTLD in patients by
organ transplanted and age
Organ
Adults (%)
Pediatric (%)
Kidney
1.0 – 2.3
1.2 – 10.1
Liver
1.0 – 2.8
4.0 – 15.0
Heart
1.0 – 6.3
6.4 – 19.5
Heart/Lung
2.4 – 5.8
6.4 – 19.5
Lung
4.2 – 10.0
6.4 – 19.5
Small bowel
20
30
Parker et al. (2010)
Presentation
Not a “typical” presentation
Usually no lymphadenopathy
May or may not have constitutional symptoms
Presenting symptoms linked to site of involvement
HEENT
GI tract
Bone marrow
Parker et al. (2010)
Diagnosis
Biopsy
Surgical excisional biopsy is preferred over core needle
biopsy
Histopathological evaluation
Imaging
Ultrasound
MRI
CT scan
PET scan
Parker et al. (2010)
Treatment/Chemotherapy
Dependent on many factors
Age
Co-morbidities
Aggressiveness of PTLD
Treatment
Reduction in immunosuppression
Antiviral therapy
Rituxan
Rituxan + combination chemotherapy (R-CHOP)
Elstrom et al. (2006)
Parker et al. (2010)
Prognosis
Caillard et al. (2006)
Anemia and Pancytopenia
Variety of causes/types
Passenger lymphocyte syndrome
Drug-induced cytopenias
Viral infections
Smith (2010)
Passenger Lymphocyte Syndrome
Caused by ABO-mismatch
Abrupt onset at 1-3 weeks
Decreased Hgb, haptoglobin
Increased LDH, bilirubin
Positive direct antiglobulin test
Treatment
Supportive care
Self-limiting after ~3 months
Smith (2010)
Drug-induced Cytopenias
Can be caused by numerous drugs
Drug not specific to SOT
Bactrim
Drugs specific to SOT
Antivirals
Immunosuppressants
Smith (2010)
Viral infections
Opportunistic infections
Parvovirus B19
CMV
Human herpes virus 6
Smith (2010)
Conclusions
PTLD
Severity, prognosis, and treatment widely vary
Biopsy, imaging, and Hematology/Oncology consult
Rituxan or R-CHOP shown to be effective but have
higher risk of side effects
Anemia and cytopenias
Many differentials to consider
Must identify source to treat appropriately
Case Study
O.L. – 7o y/o WM 3 months s/p kidney transplant
from deceased donor
Radiation nephritis (history of lymphoma 1982)
Transplant complicated by steroid induced psychosis
Maintained on low-dose Myfortic and Tacrolimus
Baseline Crt 1.3-1.5
Neutropenia – Bactrim and Valcyte held
Presents with tremor, increasing crt, thrombocytopenia,
unintentional weight loss, GI complaints
Case Study
What further tests would you order?
What things about his presentation are concerning?
Case Study
Labs
CBC
WBC 4.9
Hgb 7.9
Hct 24.6
Plt 37
BMP
Na+ 130
K+ 3.8
BUN 28
Crt 2.7
CMV
Positive for infection
Case Study
Imaging
CT chest/abd/pelvis
Stable mild adenopathy to the mesentary
Mild acute diverticulitis
New right renal transplant
No significant recurrent adenopathy below the diaphragm. No
significant thoracic adenopathy.
Enlarge mediastinal lymph node? Causing extrinsic
compression of esophagus
Bone marrow biopsy
No evidence of lymphoma
Case Study
Patient underwent esophageal ultrasound for further
assessment of lymph nodes
Abnormal mediastinal lymph node discovered
FN biopsy performed
CD 10 positive B-cell lymphoma
Kidney biopsy performed to r/o rejection
Atypical lymphocytic proliferation
Case Study
What is your differential diagnosis?
What is the next step?
What things do you need to consider in deciding on a
treatment plan?
Case Study
Patient treated with Rituxan 375mg/m2 weekly x 4
weeks
CHOP not given d/t patient’s health status, co-
morbidities
Steroids with Rituxan lowered d/t patient’s history of
steroid-induced psychosis
IV Ganciclovir for CMV infection
Immunosuppression decreased to low dose Tacrolimus
only (goal level 3-5)
Case Study
Patient tolerated Rituxan infusions well with the
exception of some transient worsening confusion d/t
steroid pre-meds
PET scan performed
Some response and reduction to lymph nodes with
Rituxan
Some residual hypermetabolism in mediastinal lymph
nodes
Patient given two options
Four additional cycles of Rituxan
Watchful waiting with repeat PET scan in 3-4 months
Case Study
Repeat PET scan 3 months later
New bulky adenopathy in the retroperitoneum
Tacrolimus discontinued and patient started on
everolimus
Patient had received one dose of Rituxan upon his
return to our clinic
Patient still not candidate for CHOP therapy
Decided to proceed with Rituxan/Treanda – received
one cycle and had confusion d/t steroids
Patient/family decided to hold off on more treatment
Case Study
Repeat PET scan 3 months later
Complete resolution of lymphoma in the chest
Marked improvement in the lymphadenopathy in the
retroperitoneum
Continued with watchful waiting
Repeat PET scan 3 months later
Aggressive recurrence with large mass in the chest and
worsening disease in the retroperitoneum
Patient decided against further treatment and opted
for comfort cares/hospice
References
Elstrom, R.L., Andreadis, C., Aqui, N.A., Ahya, V.N., Bloom,
R.D., Brozena, S.C., . . . Tsai, D.E. (2006). Treatment of
PTLD with Rituximab or Chemotherapy. American Journal
of Transplantation, 6, 569-576.
Parker, A., Bowles, K., Bradley, J.A., Emery, V.,
Featherstone, C., Gupte, G., . . . Newstead, C. (2010).
Diagnosis of post-transplant lymphoproliferative disorder
in solid organ transplant recipients – BCHS and BTS
Guidelines. British Journal of Hematology, 149, 675-692.
Smith, E. (2010). Hematologic disorders after solid organ
transplant. American Society of Hematology, 281-286.