Transplantation and Cellular Therapy 29 (2023) 46.e1 46.

e6

Transplantation and
Cellular Therapy
journal homepage: www.tctjournal.org

Full Length Article

Pediatric

Durable Engraftment and Excellent Overall Survival After CD34-

Selected Peripheral Blood Stem Cell Boost in Pediatric Patients With
Poor Graft Function Following Allogeneic Stem Cell Transplantation
Ellen Fraint1,2, Sana Farooki1,3, Elizabeth Klein1, Audrey Mauguen4, Susan E Prockop1,5,6,
Andromachi Scaradavou1,5, Kevin Curran1,5, Maria Cancio1,5, Barbara Spitzer1,5, Jaap Jan Boelens1,5,
Joseph Oved1,5, Andrew Harris1,5, Richard J O’Reilly1,5, Nancy A. Kernan1,5,*
1
Department of Pediatrics, Stem Cell Transplantation and Cellular Therapies Service, MSK Kids, Memorial Sloan Kettering Cancer Service, New York, New York
2
Division of Pediatric Hematology, Oncology, and Cellular Therapy, Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx New York
3
Division of Pediatric Hematology/Oncology, Charleston Area Medical Center, West Virginia University, Charleston, West Virginia
4
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
5
Department of Pediatrics, Weill Cornell Medicine, New York, New York
6
Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts

Article history:
Received 3 August 2022
Accepted 28 September 2022
Key Words:
Pediatric allogeneic
transplantation
Poor graft function (PGF)
CD34-selected peripheral blood
stem cell boosts
A B S T R A C T
Poor graft function (PGF) is a life-threatening complication after allogeneic stem cell transplantation (alloSCT).
Historically, outcomes of patients with PGF have been very poor, and there are no standardized approaches to
treatment. Furthermore, few outcomes after CD34-selected stem cell boost (CD34+SCB) for PGF in pediatric
alloSCT recipients have been reported. Here we report on a single center experience with CD34+SCB for PGF after
alloSCT in patients treated on the Pediatric Transplant and Cellular Therapy Service at MSK Kids, Memorial Sloan
Kettering Cancer Center. A retrospective analysis of patients transplanted for malignant and nonmalignant disor-
ders who received a CD34+SCB between 2008 to 2020 for treatment of PGF defined as the need for granulocyte
colony-stimulating factor (G-CSF) and/or packed red blood cell or platelet transfusion support with bone marrow
donor chimerism
85%. Peripheral blood stem cells from the original donor were the source for CD34+SCB. Dura-
ble complete recovery (durable CR) was defined as recovery of peripheral blood counts without recurrent need
for G-CSF or transfusion support. The main outcomes of interest were recovery of hematopoiesis and overall sur-
vival. Development of graft versus host disease (GVHD) was an additional outcome of interest. Fourteen patients
with PGF received a boost. Six patients had no known infection, while 8 patients had PGF associated with an infec-
tion. The probability of CR at 60 days was 79% (95% confidence interval [CI], 57%-100%). The overall survival at
both 2 and 5 years was 78% (95% CI, 56%-100%). One patient developed GVHD, which was fatal. No other CD34
+SCB-related toxicities were observed. While including patients with PGF as recently defined by the American
Society for Transplantation and Cellular Therapy, as well as PGF in patients with concomitant infections, we dem-
onstrate that CD34+SCB is safe and can provide for durable trilineage hematopoietic recovery and long-term sur-
vival in pediatric patients after alloSCT.
© 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights
reserved.

Poor graft function (PGF) is a life-threatening complication
after allogeneic stem cell transplantation (alloSCT) character-
ized by cytopenias, transfusion dependence, and hypocellular
marrow, which can be associated with the development of
severe infections, hemorrhage, and iron overload secondary to
Financial disclosure: See Acknowledgments on page 46.e6.
*Correspondence and reprint requests: Nancy A. Kernan, MSK Kids, Memo-
rial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
E-mail address: kernann@mskcc.org (N.A. Kernan).
multiple transfusions [1,2]. Studies have defined PGF as either
cytopenia of at least 2 cell types (absolute neutrophil count
[ANC]  500 £ 106/L; platelet count  20 £ 109/L; or hemoglo-
bin (HB)  7 g/dL) or the need for transfusion support beyond
day 28 after SCT in recipients of bone marrow (BM) or periph-
eral blood stem cells or day 42 after SCT in recipients of umbili-
cal cord blood [2 6]. Recently, a standardized definition for
PGF was established by the American Society for Transplanta-
tion and Cellular Therapy (ASTCT) as frequent dependence on
blood or platelet transfusions or growth factor support with

https://doi.org/10.1016/j.jtct.2022.09.027
2666-6367/© 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
 E. Fraint et al. / Transplantation and Cellular Therapy 29 (2023) 46.e1 46.e6 46.e2

donor myeloid and lymphoid chimerism within a desirable
target level and in the absence of other explanations, such as
disease relapse, drugs, or infections [4]. Early PGF is defined as
slow or incomplete recovery of BM function beyond day 28,
whereas late PGF is defined as a loss of BM function after ini-
tially achieving normal BM function. There are no standardized
curative approaches for patients with either type of PGF, and
supportive care with growth factors and transfusions is a
mainstay of treatment. Repeat alloSCT after preparative condi-
tioning can successfully improve PGF with response rates of
66% to 100%, but a high rate of GVHD and infectious complica-
tions lead to high non-relapse mortality (NRM) and poor over-
all survival (20%-25%) [7 9].
Infusion of an additional dose (boost) of unmodified
hematopoietic stem cells (SCB) or CD34-selected peripheral
blood stem cells (CD34+SCB) from the original donor, often
The main outcomes of interest were the achievement of CR, incidence of
GVHD, and overall survival. The cumulative incidence of CR was estimated
using an Aalen-Johansen estimator (with death and second alloSCT as com-
peting events). Overall survival (OS) was calculated as the time from CD34
+SCB to death from any cause, and surviving patients were censored at their
date of last contact. Survival rates were estimated using a Kaplan-Meier esti-
mator. The median follow-up time was calculated by reverse Kaplan-Meier.
Patients alive without recovery were censored at their date of last contact.
RESULTS
Fourteen consecutive patients who underwent alloSCT and
subsequently developed PGF received treatment with CD34
+SCBs for PGF (Tables 1-3). Of note, 6 patients had PGF as
defined by the ASTCT without infection and 8 patients had PGF
Table 1
Summary Patient Demographics

without any preceding conditioning, is a practice that has been Characteristic N = 14

used with increasing frequency to treat PGF. Retrospective Diagnosis at HCT
studies in adult recipients of alloSCT have shown that hemato- ALL in CR1 1 (7%)
poietic recovery and survival are improved after CD34+SCB ALL in CR2 3 (21%)
[3,10-18], although the definition of PGF and measurements of
MDS/CMML 1 (7%)
success are not consistent throughout these studies.
MDS 1 (7%)
The available literature on outcomes after SCB is comprised
FA-MDS/AML 1 (7%)
almost exclusively from data on adult patients, whose predis-
FA-SAA 3 (21%)
posing diseases and transplant courses differ greatly from chil-
Anemia - SAA 2 (14%)
dren. To our knowledge, only 2 published studies of post-
CGD 1 (7%)
transplantation CD34+SCB for PGF include young pediatric
patients [19,20]. Both studies demonstrated an improvement Wiskott Aldrich syndrome 1 (7%)

of PGF in children and minimal toxicity including a low inci- Age at HCT 7.8 (0.9-24.5)
dence of acute or chronic GHVD. However, neither study Donor match code
included patients whose PGF was associated with a recent MRD 1 (7%)
infectious complication. Here we report on a single-center MUD 6 (43%)
experience with CD34+SCB for PGF after alloSCT on the Pediat- MMUD 7 (50%)
ric Transplant and Cellular Therapy Service at MSK Kids, Graft source at HCT
Memorial Sloan Kettering Cancer Center. Defining PGF more CD34+ PBSC 9 (64%)
broadly than published literature to include patients with con- CD34+ BM 1 (7%)
comitant infections, we demonstrate that CD34+SCB is safe Unmodified BM 4 (22%)
and can provide for durable trilineage hematopoietic recovery Regimen intensity at HCT
and long-term survival. MA 12 (86%)
RIC 2 (14%)
METHODS
Patients Primary HCT CD34+ cell dose/kg (106) 7.18 (3.46-16.57)
An Institutional Review Board approved retrospective analysis of data
Time to engraftment (ANC
500), d 12.0 (10.0-27.0)
was performed on all patients with malignant or nonmalignant diseases who
received a CD34+SCB on the Pediatric Stem Cell Transplantation and Cellular Time between primary HCT and boost (d) 148 (50-431)
Therapy Service at MSK Kids between 2008 to 2020 for PGF. PGF was defined Donor BM % chimerism 100 (86-100)
as the need for granulocyte colony stimulating factor (G-CSF) or packed red Donor T cell % chimerism 87 (0-100)
blood cells (PRBC) or platelet transfusion support with bone marrow donor
PGF associated with infection
chimerism
85% as assessed by short tandem repeat molecular testing in the
absence of recurrent disease for patients with leukemia. Thirteen patients Yes 8 (57%)
received G-CSF mobilized peripheral blood stem cells, and one patient CMV/adenovirus/HHV6 6
(patient 1) received bone marrow from the original donors with CD34 selec-
EBV 2
tion performed by the CliniMACS CD34 reagent system (Miltenyi Biotech,
Gladbach, Germany). There was no cap on the number of CD34+ cells/kg. Mycobacterium 1
However, the number of CD3+ T cells/kg was capped at 1 £ 104/kg. No patient No infection 6 (43%)
received additional immunosuppression or GVHD prophylaxis after CD34
Treatment before boost
+SCB infusion.
None 10 (71%)
Outcomes and Statistical Analyses ATG 3 (21%)
Time to PGF was determined by decline in ANC prompting use of G-CSF ATG, Fludarabine 1 (7%)
support, need for PRBC transfusion to maintain HB
7 g/dL, or in the case of
Boost CD34+ cell dose/kg (£ 106) 7.20 (3.14-19.07)
primary thrombocytopenia defined as failure to achieve a platelet count

50,000 by day 60 or secondary thrombocytopenia defined as platelet count  ALL indicates acute lymphoblastic leukemia; AlloSCT, allogeneic stem cell
50,000 occurring after recovery (
100,000) and persisting for more than transplantation; AML, acute myelogenous leukemia; ATG, antithymocyte glob-
30 days. For patients who had primary thrombocytopenia, the time to PGF ulin; CGD, chronic granulomatous disease; CMML, chronic myelomonocytic
was set at 60 days [5,21-23]. Complete recovery (CR) was defined as achieve- leukemia; CMV, cytomegalovirus; CR1, first complete remission; CR2, second
ment of an ANC
500 £ 106/L without need for G-CSF support and HB
complete remission; EBV, Epstein Barr virus; FA, Fanconi anemia; HCT,
7 g/dL and platelet count
50 £ 109/L without transfusion support by hematopoietic cell transplant; HHV6, human herpes virus 6; MA, myeloabla-
60 days after CD34+ SCB. Durable CR was defined as having achieved CR and tive; MDS, myelodysplastic syndrome; MRD, matched related donor; MUD,
remaining in CR at time of last follow-up. All patients were monitored for matched unrelated donor; MMUD, mismatched unrelated donor; PBSC,
development of GVHD. peripheral blood stem cells; RIC, reduced intensity conditioning; SAA, severe
aplastic anemia.
46.e3 E. Fraint et al. / Transplantation and Cellular Therapy 29 (2023) 46.e1 46.e6

associated with an infection. Patient diagnoses at initial SCT

Time to
SCB (d)
included malignant (n = 7) and nonmalignant (n = 7) disorders.

278
431
142
216
146
176
243
150

142

371
56

50

70
64
The median age of the patients was 7.8 years (range 0.9-24.5
years). SCT donors included related (n = 1) and unrelated
donors (n = 13); 7 of these SCT were HLA identical and 7 were
Time to
PGF (d)
HLA mismatched with matching defined at 10 alleles. For 12

unk
367
60

60
60
60
64
60

60
60
60
60
60
46
patients the alloSCT was their first alloSCT, and for 2 patients it
was their second alloSCT (patients no. 3 and no. 10).
Details of the SCT were not available for one patient
Plt >100k

(patient no. 8) whose SCT occurred at another institution. For

Time

the other thirteen patients, the median CD34+ cell dose for

unk
n/a

n/a
n/a
n/a

n/a

n/a
n/a
n/a
n/a
n/a
(d)

21

21

15
their alloSCT was 7.18 £ 106/kg (range 3.46-16.57 £ 106/kg).
All 13 patients had recovered an ANC
500 at a median of
12 days (range 10-27 days). Despite all patients experiencing
Plt >50k

neutrophil engraftment, only 5 patients recovered a platelet

Time

unk
n/a

n/a
n/a

n/a

n/a

n/a
n/a
n/a
(d)

count
50,000 by day 60 after initial SCT. Furthermore, only 3

21

48
21

43

15
patients recovered a platelet count
100,000 at any time prior
to the CD34+SCB. The median time to PGF was 60 days (range
Plt >20k

46-367 days [one outlier]). The median time between SCT and
Time

CD34+SCB was 148 days (range 50-431 days). Bone marrow

unk
216

n/a
n/a

n/a

n/a

n/a
(d)

20

13
21
30

37

99

15
biopsies were performed in 11 of 14 patients prior to CD34
+SCB and were notably hypocellular with a median of 10% cel-
lularity (range <5%-70%). The median donor bone marrow chi-
ANC
500

merism was 100% (range 86%-100%). The median donor T cell

Time

unk

chimerism was 87% (range 0%-100%).

(d)
15
13
10
17
11
12
11

22
10
12
10
27
11

At the time of PGF, 8 of 14 patients had at least one

associated infection: CMV/adenovirus/HHV6 (n = 6), EBV
CD34/kg

(n = 2), or mycobacterium (n = 1). Infections had resolved

(£106)

16.57

14.87
13.11

in 4 patients before the SCB. Two patients on foscarnet and

3.46
5.35
3.96
8.97
4.04

8.32

6.12
10.8
3.84
7.18
unk

1 patient on ethambutol at the time of SCB resolved their

M indicates male; F, female; d, days; P/D, patient/donor; n/a, not applicable; unk, unknown; WAS, Wiskott Aldridge syndrome.

infections after the SCB. One patient died of multiorgan

failure on day 10 with adenovirus infection. Three patients
(P/D)
CMV

unk
/+

/+
+/+
+/+

+/+
+/+
+/+

+/+

+/+

+/+

had single lineage PGF requiring either G-CSF, PRBC trans-

/

/
+/

fusions or platelet transfusions; 2 patients had bilineage

PGF, and 9 patients had trilineage PGF. Two patients with
MMUD

MMUD

MMUD

MMUD

MMUD

MMUD
MMUD

trilineage involvement had no response to romiplostim

Match
Donor

MUD
MUD
MUD

MUD

MUD

MUD
MRD

(patient 3) or eltrombopag (patient 4). Ten patients had no

lymphodepleting treatment prior to CD34+SCB; 8 of these
10 patients had 90% to 100% donor T-cell chimerism. Three
Unmodified BMT
Unmodified BMT
Unmodified BMT

Unmodified BMT

patients received ATG alone (donor T-cell chimerism 0%,

53%, and 66%) and 1 patient with 3% donor T-cell chime-
CD34+ PBSC
CD34+ PBSC
CD34+ PBSC

CD34+ PBSC
CD34+ PBSC
CD34+ PBSC
CD34+ PBSC
CD34+ PBSC
CD34+ PBSC
CD34+ BM

rism received ATG and fludarabine. The median SCB CD34+

Source of
Primary
alloSCT

cell dose was 7.20 £ 106/kg (range 3.14-19.07 £ 106). The

median SCB CD3+ cell dose cell was 3.44 £ 103/kg (range
0.45-8.82 x 103/kg). Nine patients received freshly collected
products and 5 patients received products that had been
Intensity

cryopreserved at the time of the primary alloSCT.

The probability of CR following CD34+SCB at 60 days after
MA

MA
MA
MA
MA
MA

MA
MA
MA
MA
MA
MA
RIC

RIC

CD34+SCB was 79% (95% CI, 57-100%; Figure 1A). The median
time to CR for 11 of 12 patients with CR was 20 days (range 7-
42 days). The twelfth patient with chronic granulomatous dis-
FA-MDS/AML

MDS/CMML

ease recovered hematopoietic function at day +166. All

Diagnosis

ALL CR2

ALL CR2

ALL CR1

ALL CR2
FA-SAA

FA-SAA

FA-SAA

patients with single or bilineage PGF and 7 of 9 patients with

WAS

MDS
CGD
SAA

SAA

trilineage PGF achieved CR (total 12 of 14 patients). Complete

recovery was durable as none of these patients required
subsequent growth factor or transfusion support in the
Individual Patient Demographics

Sex

absence of the development of autoimmune hemolytic ane-

M

M
M

M
M

M
F
F

mia (patient no. 10). Of the two patients with persistent

PGF, 1 had a successful second SCT (patient #2) and 1 died
13.6

14.5

24.5

10.1
20.6
20.5
Age
(yr)

of multiorgan failure (patient no. 3). Despite achieving CR,

7.2

0.9

3.3
3.8

6.8
7.8
7.8
7.3

1 patient died from the subsequent development of auto-

immune hemolytic anemia (patient no. 10) and one patient
died from acute GVHD (patient no. 13) that developed after
Patient
Table 2

CD34+SCB. Patient no. 13 was the only patient to develop

10
11
12
13
14
1
2
3
4
5
6
7
8
9

GVHD; 2 patients with a prior history of GVHD did not

Table 3
Individual Patient Evaluation and Outcome

Patient Infection Treatment for Infection h/o GVHD BM Cellularity BM Donor T cell Donor GCSF PRBC Tx Plt Tx Number Treatment SCB SCB Outcome
(%) chimerism (%) Chimerism (%) dep dep Lineages before SCB CD34/kg CD3/kg
Involved before SCB (£106) (£103)
1 CMV, Ganciclovir, Foscarnet, N 40 100 91 N Y N 1 none 4.32 0.45 CR Alive 64.9 mo
BK virus Cidofovir off treatment
2 EBV Rituximab Off treatment N 30 100 53 Y Y Y 3 ATG 16.08 3.26 PGF 2nd SCT Alive 99.4 mo
3 Adenovirus Cidofovir On treatment Y <5 95 100 Y Y Y 3 none 5.65 6.86 PGF died day 10 MOF
4 CMV, Ganciclovir, Foscarnet, Y 60 96 98 Y Y Y 3 none 9.85 3.00 CR alive 65.6 mo
Adenovirus Cidofovir Off treatment
5 CMV, Foscarnet On N <5 100 100 Y N Y 2 none 3.14 2.96 CR alive 119.8 mo
Adenovirus, maintenance
RSV

E. Fraint et al. / Transplantation and Cellular Therapy 29 (2023) 46.e1 46.e6

6 EBV, CMV Rituximab, Ganciclovir, N nd nd 12 Y N N 1 none 18 3.62 CR alive 55.4 mo
Foscarnet, EBV-Cytotoxic
T cells Off treatment
7 Mycobacterium Ethambutol N 70 100 100 Y Y Y 3 none 4.16 7.23 CR alive 119.8 mo
On treatment
8 CMV, HHV6 Ganciclovir, Foscarnet N nd nd nd Y Y Y 3 none 5.27 5.93 CR alive 18.9 mo
CMV-Cytotoxic
T cells On treatment
9 None None N 40 100 87 N Y Y 2 none 3.7 3.01 CR Alive 29.7 mo
10 None None N <5% 100 24 Y Y Y 3 none 19.07 3.92 CR died day 702 AIHA
11 None None N 9 88 0 Y Y Y 3 ATG 4.05 4.25 CR alive 34.6 mo
12 None None N nd 100 95 N N Y 1 none 10.04 8.82 CR alive 109.5 mo
13 None None N 10 88 66 Y Y Y 3 ATG 8.97 2.72 CR died day 315 GVHD
14 None None N 9 86 3 Y Y Y 3 ATG, 8.74 2.64 CR alive 60.3 mo
fludarabine

AIHA indicates autoimmune hemolytic anemia; h/o, history of; nd, not done; MOF multi-organ failure; PRBC Tx dep, packed red blood cell transfusion dependent; Plt Tx dep, platelet transfusion dependent; RSV, respiratory syncytial
virus.

46.e4
46.e5 E. Fraint et al. / Transplantation and Cellular Therapy 29 (2023) 46.e1 46.e6
survival
Figure 1. Results in patients receiving CD34-selected stem cell boost. (A) The cumulative incidence of complete recovery by 60 days after CD34+SCB was 79% (95% CI,
57%-100%). (B) The overall survival after CD34+SCB at both 2 years and 5 years was 78% (95% CI, 56%-100%).
experience a flare of GVHD after CD34+SCB. No additional
toxicity related to CD34+SCB was noted.
Six patients had recovered an absolute CD4+ T cell count
>200 cells/mL before the SCB. Eight patients had not immune
reconstituted before the SCB; 5 patients who achieved CR and
survived experienced full immune reconstitution whereas the
3 patients who died did not immune reconstitute before
death.
The overall survival following CD34+SCB at both 2 and
5 years was 78% (95% CI, 56%-100%; Figure 1B). The median fol-
low-up time from SCB was 60.3 months (range 3.4 months to
10.0 years).
DISCUSSION
In this retrospective study, we report excellent survival
with very low toxicity in pediatric recipients of CD34+SCBs for
treatment of PGF, about half of whom had an associated infec-
tion. Hematologic responses were common with a CR rate of
79% and occurred at a median of 20 days after CD34+SCB, lead-
ing to excellent OS of 78% at 5 years. These 14 patients demon-
strated a markedly improved outcome compared to the
historically abysmal fate of patients with PGF [7 9]. Overall,
CD34+SCBs were well tolerated; two patients with a prior his-
tory of aGVHD did not have a flare of aGVHD (patients no. 3
and no. 4), and only 1 patient developed any level of GVHD,
although it was fatal.
Existing literature has defined PGF variably, using different
thresholds for cytopenias and requiring different numbers of
affected lineages, with most authors describing at least 2
affected lineages for inclusion [6]. However, most recently,
ASTCT definitions have been published that do not specify
multilineage involvement [4]. Although most of our patients
had 2- or 3-lineage involvement, 3 patients with single-lineage
involvement were included in our study, because the long-
term need for G-CSF support, PRBC transfusions, or platelet
transfusions can lead to increased morbidity and NRM. Our
study demonstrates the wide applicability of therapeutic CD34
+SCB, as all those with single (n = 3) or bilineage (n = 2) PGF,
and 7 of 9 patients with trilineage PGF had CR (total 12 of 14
patients).
Some prior literature with adult patients demonstrates
similar outcomes to our cohort. Shahzad et al. [24] published a
systematic review and meta-analysis of 7 studies with 209
adult patients with leukemia who received CD34+SCB for
treatment of PGF. In their meta-analysis, the median time
from alloSCT to CD34+SCB was 138 days (range 113-450 days),
like the time period reported in our series of 163 days (range
50-431 days). Similarly, their complete hematologic response
rate was 72% (95% CI, 63%-79%), which is analogous to the CR
rate of 79% (95% CI, 57%-100%) in our study. For the 209 adult
patients, OS ranged from 80% at 1 year to 40% at 9 years with
NRM of 27% and death due to relapse in 17% of patients. In our
series, the OS was 78% (95% CI, 56%-100%) at 5 years. Because
of the heterogeneity of the adult patients in the study by Shah-
zad et al. [24], pooled analysis based on donor type and other
parameters could not be done. However, the authors con-
cluded that CD34+SCB infusion could provide a safe and effec-
tive treatment option in adult patients with PGF after alloSCT.
Literature describing pediatric patients is more limited.
Most notably, Mainardi et al. [19] reported a single-center
study of CD34+SCBs that included pediatric patients (n = 50,
median age 11.8 years, range 0.33-38.98 years). They included
patients with at least bilineage cytopenias or dependence on
transfusion with full donor chimerism in the absence of dis-
ease relapse or GVHD. Concomitant infection in these patients
was not addressed. Although 78.8% of their patients had an
 E. Fraint et al. / Transplantation and Cellular Therapy 29 (2023) 46.e1 46.e6
improvement in 1 or 2 lineages, only 36% achieved complete
hematologic recovery. Their 5-year OS was low (38.67%)
because of NRM (24% of total) and relapse (28% of total). It is
not clear why they had such different results from our study,
but there are some notable differences between our patient
populations. The outsized contribution of patients with malig-
nant disorders in their cohort (nearly all their patients, with
almost 30% not in remission at the time of initial transplanta-
tion) as compared with our cohort, only half of whom had
malignancy, likely plays a role in these divergent outcomes,
because relapse led to a large proportion of their patient
deaths. Our study demonstrates that CD34+SCB can be both
effective and well tolerated in pediatric patients with malig-
nant or nonmalignant disorders experiencing PGF.
The incidence of acute GVHD among the 209 adult
recipients of CD34+SCB in the meta-analysis by Shahzad
et al. [24] was 17% (95% CI, 13%-23%) [24].In our small
pediatric series, only one patient developed any level of
aGVHD, although it was fatal. No additional toxicities
related to the CD34+SCB were observed in any other
patients. Using CD34+SCB as a tool to correct PGF after
alloSCT is attractive, especially in comparison to the option
of repeat SCT. Repeat alloSCT after preparative conditioning
can successfully improve PGF with response rates of 66% to
100%, but this comes at the expense of additional exposure
to cytotoxic medications with inherent short and long-term
associated risks and toxicities, GVHD, infectious complica-
tions, and other toxicities that contribute to NRM.
Our study is limited by the single institution focus, small
sample size and retrospective nature, but it provides insight
on the utility of CD34+SCB for ameliorating cytopenias in pedi-
atric patients with PGF post alloSCT. Our cohort demonstrates
the use of CD34+SCB in a wide range of patient types, including
those transplanted for malignant and nonmalignant disorders;
with myeloablative or reduced intensity conditioning; with
either HLA matched or HLA mismatched donors; and with con-
comitant viral or mycobacterial infections. Our cohort is too
small to answer questions about whether immunosuppression
prior to CD34+SCB improves outcomes, but most of the
patients here, as in other studies, did not receive cytoreduction
or lymphodepletion before the infusion of CD34+SCB.
Although PGF is not a common complication of transplanta-
tion, exploring best practices in treatment of PGF is important
because of the high morbidity and mortality associated with
PGF. This study demonstrates that for pediatric allogeneic SCT
recipients with PGF and high donor bone marrow chimerism
of at least 85%, whether idiopathic or associated with an infec-
tion, CD34-selected peripheral blood stem cell boost is safe
and can provide for durable trilineage engraftment and long-
term survival.
ACKNOWLEDGMENTS
The authors acknowledge the editorial assistance of Joe
Olechnowicz, Editor, MSK Kids.
Financial disclosure: Supported by grants from the NIH/NCI
Cancer Center Support Grant P30 CA008748.
Conflict of interest statement: There are no conflicts of inter-
est to report.
Authorship statement: All authors provided contributions to
the concept or design of the work; or the acquisition, analysis,
or interpretation of data for the work. E.F. and N.A.K. wrote the
initial drafts and all authors provided critical review and revi-
sions for intellectual content. All authors approved the submit-
ted version.
46.e6
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