Late Pneumocystis Pneumonia After HSCT: Atypical Presentation and Lack of Correlation with CD4 Count

Duration of Pneumocystis pneumonia (PCP) prophylaxis after allogeneic HSCT is not well defined. Guidelines recommend at least six months, and longer for patients on immunosuppression. We report six cases of PCP that happened late after allo-HSCT (median 36 months, range 19-80). All had received peripheral blood HSCT: three from matched sibling donors (MRD), and three from matched unrelated donors (MUD) (the latter with alemtuzumab conditioning). At the time of PCP, three patients (#3, #4, #5) were not on immunosuppression and had no active graft versus host disease (GVHD). Their mean CD4 T cell count was 569 (range 411-664). The other three had late-acute (#6, post-DLI) or chronic (#1 and #2) GVHD. Only #1 was on prednisone (< 0.5 mg/kg); #2 and #6 were on MMF alone. Their mean CD4 T cell count was 210 (range 86-380). #1 and #5 were on PCP prophylaxis (dapsone, atovaquone).

Clinical presentation was atypical. Subacute fever without shortness of breath (SOB) was most common. Patient #1 was asymptomatic, with diffuse infiltrates found on restaging chest CT. Only #2 presented with acute SOB and hypoxemia. All patients had ground-glass opacities, but these were patchy/multifocal (n=4) rather than diffuse (n=2). PCR was more sensitive than DFA or GMS. Response to TMP/SMX (± steroids) was uniformly positive.

Conclusion: PCP may occur late after transplant, even in the absence of immunosuppressive therapy, active GVHD or CD4-T lymphopenia. Patchy ground-glass opacities and nonspecific infiltrates are the common radiologic feature. Post-transplant CD4 count does not seem to be useful to predict PCP or the need for prophylaxis. It is possible that a qualitative immune T cell defect accounts for late PCP.

Patient # Age, gender	1 46M	2 35M	3 51M	4 46M	5 55M	6 54M
Disease	DLBCL	HD	DLBCL	MZL	TCL	CLL
Months after Tx at PCP	36	58	36	19	80	27
HSCT donor	MUD (campath)	MRD	MUD (campath)	MUD (campath)	MRD	MRD
aGVHD	GI	No	GI, skin	No	Skin	Skin, liver post-DLI
cGVHD	Mouth, upper GI, eyes	Extensive	No	No	No	No
GVHD Rx	Prednisone, topical steroids	MMF, azithromycin, montelukast	None	None	None	MMF, topicals
CD4 (334-1556)	86	380	411	631	664	164
PCP prophylaxis	Dapsone	No	No	No	Atovaquone	No
Presentation	Asymptomatic	Acute SOB cough	Subacute fever	Subacute fever	Subacute fever; cough	Subacute fever; cough
CT	Diffuse reticular and ground glass opacity	Ground glass opacities, focal consolidation in both upper lobes, and RML	Diffuse multifocal ground glass and reticular opacities in both lungs.	Bilateral ground glass infiltrates.	Multi focal nodular and diffuse infiltrates.	RLL consolidation and patchy ground glass opacities in RML and LLL.
BAL	GMS+ DFA+ PCR+	GMS+ DFA+ PCR+	GMS+ DFA+ PCR+	GMS- DFA- PCR+	GMS- DFA- PCR+	GMS- DFA+ PCR+