Blood Bank questions

2019_Ye_RiskofRBCalloimmunizationinMMpatientstreatedbyDara.pdf

Home >Education homework help >Blood Bank questions

Vox Sanguinis (2020) 115, 207–212

Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab Zhan Ye, Laurie A. Wolf, Daniel Mettman & Fred V. Plapp University of Kansas Medical Center, Kansas City, Kansas, USA

Received: 29 March 2019, revised 11 October 2019, accepted 21 October 2019, published online 14 November 2019

Background Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and inter- feres with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA.

Materials and methods A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty-six MM patients received transfusion but not DARA were studied as control group.

Results Totally 184 Ab screens were done on 45 patients transfused with ABO- Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screen- ing positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period.

Conclusions Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA-associated difference in the alloimmunization risk. No significant dif- ference in alloimmunization is detected between ABO-Rh compatible and pheno- typically matched transfusion.

Key words: RBC antigens and antibodies, Serological testing, Transfusion medi- cine, Immunohaematology.

Introduction

Daratumumab (DARA) is a human immunoglobulin (Ig) G1

monoclonal antibody (Ab) that recognizes highly expressed

CD38 on multiple myeloma (MM) cells [1]. In November

2015, the US Food and Drug Administration (FDA)

approved DARA as monotherapy for relapsed/refractory

MM patients who had already received three previous treat-

ments. One year later, DARA received additional FDA

approval as combination therapy with lenalidomide or

bortezomib and dexamethasone for MM patients who had

received at least one prior therapy [2–4].

DARA in patients’ plasma also binds weakly expressed

CD38 on reagent human red blood cells (RBC). Although

it does not affect ABO/Rh typing [5], DARA causes posi-

tivity of indirect antiglobulin tests (IAT) performed at

37°C. During phase I and II trials of DARA, plasma of all DARA-treated patients demonstrated weak (1+) panreac- tivity with all RBC panels using anti-human globulin (gel,

tube and solid phase), for up to 6 months [5,6].

Many methods have been developed to negate DARA

interference including destruction of CD38 on reagent

RBC by dithiothreitol (DTT) or proteolytic enzymes such

as trypsin and papain [5,7]; masking CD38 with F(ab’)2

fragments of DARA [8]; using CD38-negative reagent

Correspondence: Zhan Ye, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 4000 Cambridge Street, Kansas City, Kansas 66160, USA. E-mail: [email protected]

207

https://orcid.org/0000-0003-2378-3813

mailto:

RBC such as cord RBC [9]; and neutralizing DARA in

patient plasma with anti-DARA idiotype antibody or

recombinant human soluble CD38 [5,6]. DTT denaturation

of CD38 on reagent RBC by disruption of disulphide

bonds in its extracellular domain is the most widely

adopted method to negate DARA interference worldwide

[10]. The other methods are unlikely to replace DTT

because of their higher cost, lack of availability or thor-

ough validation, or destruction of multiple clinically sig-

nificant antigens (Ag) on reagent RBC.

DTT denatures Ag from nine blood group systems

(Dombrock, Indian, John Milton Hagen, Kell, Knops,

Landsteiner-Wiener, Lutheran, Raph, Cartwright) and

interferes with detection of their corresponding Abs in

patients’ plasma [6]. Most of these Abs are rarely encoun-

tered, with the exception of anti-Kell Ab, which is clini-

cally significant. For this reason, Kell-negative units are

provided unless the recipient is Kell-positive. Hosokawa

et al. recently demonstrated that a lower concentration of

DARA (0�01 mol/L) preserved detection of anti-Kell while negating DARA interference [11].

Risk of alloimmunization and potential Ab-mediated

haemolysis could be significantly reduced through pheno-

typically or genotypically matching the most common

clinically significant RBC Ags such as Rh, Kell, Kidd,

Duffy and MNS. DARA-treated patients transfused with

phenotypically or genotypically matched RBC have not

experienced Ab-mediated haemolysis or alloimmunization

[12,13]. To ensure accuracy, RBC phenotype must be

determined prior to the initiation of DARA therapy and in

the absence of a positive DAT and transfusion in the prior

3 months. Genotyping, which is usually performed by ref-

erence laboratories, incurs extra expense and prolonged

turnaround time [12]. Cushing et al. report that the

annual cost of transfusion per DARA-treated patient is

almost doubled by using universal genotyping, compared

to a DTT-based algorithm with selective genotyping [14].

Furthermore, the availability of phenotypically or geno-

typically matched units may be limited.

Our hospital transfusion service received its first

DARA-treated patient specimens in July 2015, prior to

DARA’s FDA approval. Since then, 145 patients have

been treated with DARA through December 2018. To our

knowledge, almost all published studies regarding DARA

interference in pre-transfusion testing have focused on

resolution of DARA-induced panreactivity. While one

study has reported the incidence of RBC alloimmunization

in a relatively small number of DARA-treated patients,

direct correlation between transfusion and alloimmuniza-

tion was not investigated [14]. Therefore, a retrospective

study of the serological profile and transfusion history of

all MM patients treated with DARA in our hospital was

undertaken. The aim of this study was to evaluate the risk

of RBC alloimmunization in DARA-treated patients after

transfusion with either ABO-Rh compatible or phenotypi-

cally matched RBCs.

Material and method

Patients

A total of 145 MM patients were treated at the University

of Kansas Hospital (TUKH) with DARA (Darzalex; Jans-

sen-Cilag Pty Ltd) from July 2015 to December 2018.

TUKH followed the indications and protocol of DARA

treatment described in the FDA Darzalex prescribing

information [15]. The patients’ history of DARA adminis-

tration including initiation date, end date, RBC transfu-

sion, stem cell transplant history and blood bank

serological results (ABO-Rh typing, Ab screen and identi-

fication) were collected. To compare alloimmunization

rate, the same information was also collected for MM

patients treated at TUKH from January 2013 to June 2015

before DARA was available. A total of 328 patients were

managed by chemotherapy and stem cell transplant only.

Study period

The study period of DARA group always started with the

first dose of DARA. However, the end-point varied based

on RBC Ab screen results, which included the following

two conditions: (1) 6 months after the last DARA dose if

patients’ Ab screen remained negative or (2) the first neg-

ative Ab screen after the last DARA dose if the Ab screen

had ever been positive. If patients passed away prior to

these end-points, their expiration dates became the end-

point. The study period of the non-DARA group started

from their first TUKH visit to the last one between Jan-

uary 2013 and June 2015.

Blood typing and antibody screen

Patient blood typing and a two-red cell Ab screen were

performed utilizing tube tests and gel column agglutina-

tion technology, respectively. (ORTHOTM ID-Micro Typing

System gel column technology, Ortho Clinical Diagnos-

tics, Raritan, NJ with Panoscreen, Immucor, Norcross,

GA.)

Ab identification was performed on all patients with a

positive Ab screen in tube tests with low-ionic-strength

saline (LISS) and panel red cells (Panocell-10 or -20,

Immucor, Norcross, GA). Direct antiglobulin testing (DAT)

was performed on all samples with a positive autocontrol.

All DATs were performed with polyspecific antiglobulin

reagent and subsequently tested with monospecific anti-

IgG and anti-C3b and anti-C3d reagents, if positive. Acid

208 Z. Ye et al.

eluates were prepared from patient samples if not per-

formed in the preceding six months or if the strength of

the reactivity increased.

All cases with positive Ab screens in the DARA Transfu-

sion Group were tested with 0�2 M DTT-treated RBCs to identify RBC alloantibodies either in our hospital or a refer-

ence laboratory. DTT treatment method was validated in

our hospital on 1 July 2017. A detailed method of DTT

treatment of RBCs is described in AABB Technical Manual

and a previous publication [5,16]. Quality control was per-

formed using untreated and DTT-treated cells tested with

anti-Kpb to verify the denaturation of Kell system Ags.

Subsequent Ab identification included testing the reactive

plasma with DTT-treated RBCs in tube tests with LISS.

RBC transfusion

Red blood cells transfusion history was monitored

throughout the study period for both DARA and non-

DARA groups. There were two types of transfused RBC

units according to the degree of RBC Ag match: (1) ABO-

Rh compatible and (2) ABO compatible plus phenotypi-

cally matched for Rh, Kell, Duffy, Kidd and Ss.

The electronic crossmatch was performed on non-

DARA group when no historical or current alloantibody

was detected. A serologic crossmatch was performed in

tube tests, including immediate spin and antiglobulin

phases of testing with LISS, on DARA group and any

patients with historical or detectable alloantibodies.

Donor units selected for non-DARA group were ABO-

Rh compatible and negative for corresponding Ags if they

had any historical or detectable alloantibodies. Prior to

validation of DTT method in our hospital, all patients in

the DARA group received ABO compatible plus phenotyp-

ically matched RBCs. After that, they all received ABO-Rh

compatible units negative for K Ag and corresponding

Ags if an alloantibody was detected.

Statistical analysis

The Fisher’s exact test was conducted by Software R [17].

Odds ratio with 95% confidence intervals (CI) was obtained

through adding 1 s to all elements in the contingency table

to estimate the variance due to the 0 incidence in all groups

[18]. Significance level was set at 0�05.

Results

Patients

From May 2015 to December 2018, a total of 145 patients

were treated with DARA at TUKH. Twelve patients were

excluded from analysis: 10 patients had missing records

of initiation or end date of DARA treatment, 1 patient

expired 10 days after the initiation of DARA without an

Ab screen being performed and 1 patient only received

one treatment and then switched to elotuzumab due to

intolerance of DARA. Among 133 patients with complete

records, 45 patients were transfused with RBC (DARA

Transfusion Group) during the study period while 88

patients were not.

A total of 328 MM patients were treated at TUKH from

January 2013 to June 2015, among whom 46 patients

received RBC transfusion (Non-DARA Transfusion Group).

The demographics of both groups are summarized in

Table 1.

Blood transfusion

Two hundred and forty-six units of RBCs were transfused

to 45 patients in the DARA Transfusion Group: 32

patients only received ABO-Rh compatible RBCs, 1

patient only received ABO compatible plus phenotypically

matched RBCs and 12 were transfused with both ABO-Rh

compatible and ABO compatible plus phenotypically

matched RBCs. All 46 patients in the Non-DARA Transfu-

sion Group received 284 units of ABO-Rh compatible

RBCs without phenotypical match. Two patients with RBC

alloantibodies in this group received ABO-Rh compatible

plus Ag-negative RBCs. The number of patients and RBC

units transfused is listed in Table 2.

Antibody screen and identification

The results of Ab screen and identification of both the

DARA Transfusion Group and Non-DARA Transfusion

Group are summarized in Table 3.

Two of 46 patients in the Non-DARA Transfusion

Group had a positive Ab screen (anti-Jka and anti-K) at

the beginning of study period. Both antibodies were gen-

erated after transfusion prior to treatment at our hospital.

The Abs persisted after transfusion of ABO compatible

plus Ag-negative RBCs during the study interval. No new

alloantibodies were detected during the study period.

Table 1 Patient demographics

Number of patients Age

Gender ratio (female/male)

Percentage of death

DARA

transfusion

group

45 65�1 – 10�6 21/24 27% (12/45)

Non-DARA

transfusion

group

46 59 – 10�1 24/22 20% (9/46)

RBC alloimmunization and Daratumumab 209

In the DARA Transfusion Group, none of 45 patients

had a positive Ab screen prior to the first DARA treat-

ment. Forty-two of the 45 patients developed positive Ab

screens during DARA treatment and 3 patients’ Ab

screens remained negative. The reason for the negative

Ab screens in these 3 patients was not determined but it

was noted that all of them passed away within 3 weeks

after the last DARA dose.

The duration of Ab screen positivity varied markedly,

ranging from 25 days to 5 months after the last DARA

dose. Altogether, 184 Ab screens were performed after the

initiation of DARA on these patients and none of them

had detectable alloantibodies after DTT treatment. Eight

patients in the DARA Transfusion Group had an addi-

tional 55 Ab screens performed after the study period (ad-

ditional 1–9 months) and none of them were positive.

As described in Table 2, patients in the DARA Transfu-

sion Group received either ABO-Rh compatible RBCs,

ABO compatible plus phenotypically matched units or

both. They also received an additional 41 units of ABO-

Rh compatible RBC following the study period. None of

these patients developed alloantibodies, even after pro-

longed transfusion, regardless of which RBC selection

strategy was chosen.

Alloimmunization risk comparison

None of the 45 patients in the DARA Transfusion Group

and 46 patients in the Non-DARA Transfusion Group who

received ABO-Rh compatible units developed alloantibod-

ies. Fisher’s exact test showed no significant difference in

the risk of developing alloantibody between the DARA

Transfusion Group and Non-DARA Transfusion Group.

Odds ratio (95% CI) was 1�04 (0�01, 83�65), P = 1. In the DARA Transfusion Group, 181 ABO-Rh compati-

ble units and 65 ABO compatible plus phenotypically

matched units were transfused. No alloantibody was

detected post-transfusion with either type of blood. There

was no significant difference in the risk of developing

alloantibody between the ABO-Rh compatible units and

ABO compatible plus phenotypically matched units. Odds

ratio (95% CI) was 0�37 (0�004, 29�05), P = 0�47.

Discussion

Decreased risk of RBC alloimmunization has been

reported in patients with immunosuppression. Extensive

studies of Rh-D-negative patients with hematopoietic pro-

genitor cell transplantation, solid organ transplantation

and HIV infection did not detect any anti-D alloimmu-

nization after transfusion of Rh-D-positive RBCs [19–21].

Another study reported that the frequency of anti-D for-

mation was only 20% in hospitalized patients [22], while

it was more than 80% in immunocompetent individuals.

Therefore, the low alloimmunization rate of non-DARA

Table 2 Profile of transfused RBCs

DARA transfusion group

Non-DARA transfusion group

ABO-Rh compatible

RBCs only

109 units (32 patients) 284 units (All 46

patients)

2 patients with

positive Ab screen

received

Ag-negative RBCs: 1

unit of Jka-negative

and 2 units of

Kell-negative

ABO compatible plus

phenotypically

matched RBCs only

3 units (1 patient) None

Both ABO-Rh

compatible and ABO

compatible plus

phenotypically

matched RBCs

72 units of ABO-Rh

compatible RBCs, 62

units of ABO

compatible plus

phenotypically

matched RBCs (12

patients)

None

Table 3 Ab screen and Ab identification

Ab screen before first DARA dose

Ab screen during study period

New alloantibody detected

Total Ab screen performed

Positive Ab screen

Negative Ab screen

DARA Transfusion

Group (45 patients)

Negative 184 180 (42 patients) 4 (3 patients) None (after DTT treatment)

Non-DARA Transfusion

Group (46 patients)

Two patients had positive Ab

screen from previous transfusion

(anti-Jka and anti-K)

301 5 (2 patients) 296 (44 patients) None (anti-Jka and anti-K

persisted in those two patients)

210 Z. Ye et al.

Transfusion Group is expected. Although no new alloanti-

bodies were detected during study period, the preexisting

anti-Jka and anti-K were generated after transfusion dur-

ing chemotherapy.

Our study showed no significant difference in alloim-

munization risk between the DARA Transfusion Group

and Non-DARA Transfusion Group, probably due to the

low alloimmunization rate of MM patients receiving

chemotherapy. However, two patients in the non-DARA

group developed alloantibodies before the study period

but no alloantibodies were detected in the DARA group,

even after multiple transfusions. Although we did not

detect a difference of red cell alloimmunization in the

DARA group, others have reported RBC antibody suppres-

sion using DARA. Schuetz et al. recently reported that

DARA was effective in treating paediatric patients with

autoimmune haemolytic anaemia post-hematopoietic stem

cell transplantation [23]. Chapuy et al. also reported a

case of delayed red cell engraftment caused by persis-

tently high titre anti-donor anti-A which was successfully

treated by DARA [24].

Our study had two major limitations. First, sample size

of the DARA Transfusion Group included only 45

patients. Despite the wide usage of DARA since its FDA

approval in 2015, the absolute number of patients

remains small and the majority of them do not require

transfusion. A longer period of data collection may be

necessary to increase statistical power. Second, our study

was done in a single hospital but RBC alloimmunization

rates may vary significantly among different institutions.

Cushing et al. reported a RBC immunization rate of

26�4% (24 of 91 patients) in their DARA-treated group [14] but we did not detect any new RBC antibody forma-

tion. This difference may result from variation in disease

stages, MM management strategy and RBC immunization

rates in different ethnic groups. A multicenter study

should be undertaken to more accurately assess the

immunization rate of those patients.

Currently, there is no consensus regarding pre-transfu-

sion testing for patients being treated with DARA. Two

similar algorithms have been published recently [12,25].

Both recommended transfusion of uncrossmatched O or

ABO compatible RBCs when patients needed emergent

transfusion. For routine transfusions, pre-transfusion

workups of DARA panreactivity included DTT treatment

of reagent RBC and selection of Kell-negative RBC. If the

DTT method was not available, then phenotypically or

genotypically matched RBCs were selected for transfusion.

When neither DTT treatment nor phenotyping/genotyping

was available, then patients’ samples were sent to a

reference laboratory. To avoid delay, Lancman et al. sug-

gested obtaining patients’ phenotype or genotype prior to

the initiation of DARA therapy [12].

Considering the low incidence of RBC alloimmuniza-

tion in this patient population and lacking apparent bene-

fit of phenotypically matched transfusion, the pre-

transfusion workup of DARA patients could be simplified.

The following protocol is recommended based on our cur-

rent findings: (1) maintain a current database of patients

being treated with DARA; (2) perform Ab screen and

identification prior to the initiation of DARA therapy; (3)

use DTT treatment for patients demonstrating panreactiv-

ity during and after DARA treatment if they have a newly

detected or historical alloantibodies prior to the initiation

of DARA; (4) consider eliminating DTT treatment if pan-

reactivity of Ab screen and identification tests is present

during and within two weeks after the last dose of DARA

treatment on patients without current or historical alloan-

tibodies before the initiation of DARA; and (5) forgo phe-

notyping or genotyping at any time during and after

DARA treatment.

A 2-week interval was chosen because DARA interfer-

ence disappeared as early as 25 days after the last dose.

Regular Ab screen and identification with DTT treatment

should be resumed after this window.

Besides DARA, several other anti-CD38 monoclonal

Abs, such as isatuximab (chimeric IgG kappa Ab),

MOR202 (human IgG1 lambda Ab) and TAK079 (human

IgG1 Ab), are currently in different phases of clinical tri-

als [26]. Panreactivity in pre-transfusion tests has also

been found with anti-CD38 monoclonal Abs other than

DARA [6]. A new human monoclonal IgG4 Ab, anti-CD47

(Hu5F9-G4), is also in clinical trials for the treatment of

haematologic and solid malignancies. Plasma from

patients on anti-CD47 shows panreactivity in all phases

of pre-transfusion testing (IS, room temperature, 37 C,

and IAT with or without enhancement), including ABO

reverse typing. Multiple RBC alloadsorptions and/or mon-

oclonal gamma-clone anti-IgG were the only interven-

tions that eliminated panreactivity [27].

The introduction of more and more therapeutic mono-

clonal Abs will continue to challenge transfusion practice.

Transfusion medicine specialists need to be aware of

potential interference by these new drugs. Extensive test-

ing for compatibility is necessary to prevent haemolytic

transfusion reactions. However, determining the risk of

RBC alloimmunization in patients treated with these novel

therapies may help to eliminate some time-consuming

tests. Experience with the management of DARA-induced

panreactivity should facilitate these evaluations.

RBC alloimmunization and Daratumumab 211

References 1 Lin P, Owens R, Tricot G, et al.: Flow

cytometric immunophenotypic analysis

of 306 cases of multiple myeloma. Am

J Clin Pathol 2004; 121:482–8

2 McKeage K: Daratumumab: first global

approval. Drugs 2016; 76:275–81

3 Lokhorst HM, Plesner T, Laubac JP,

et al.: Targeting CD38 with daratu-

mumab monotherapy in multiple mye-

loma. N Engl J Med 2015; 373:1207–19

4 US Food and Drug Administration.

Resource for approved drugs—Daratu-

mumab, 2016. [Available at https://

www.fda.gov/Drugs/InformationOnDrugs

/ApprovedDrugs/ucm530249.htm (ac-

cessed February 14, 2019).].

5 Chapuy CI, Nicholson RT, Aguad MD,

et al.: Resolving the daratumumab

interference with blood compatibility

testing. Transfusion 2015; 55(6 Pt

2):1545–54

6 Oostendorp M, Lammerts van Bueren

JJ, Doshi P, et al.: When blood trans-

fusion medicine becomes complicated

due to interference by monoclonal

antibody therapy. Transfusion 2015;

55(6 Pt 2):1555–62

7 Carreno-Tarragona G, Cedena T, Mon-

tejano L, et al.: Papain-treated panels

are a simple method for the identifica-

tion of alloantibodies in multiple mye-

loma patients treated with anti-CD38-

based therapies. Transf Med 2018;

29:193–196.

8 Selleng K, Gebicka PD, Thiele T: F(ab’)

2 Fragments to Overcome Daratu-

mumab Interference in Transfusion

Tests. N Engl J Med 2018; 379:90–91

9 Schmidt AE, Kirkley S, Patel N, et al.:

An alternative method to dithiothreitol

treatment for antibody screening in

patients receiving daratumumab.

Transfusion 2015; 55:2292–3

10 Chapuy CI, Aguad MD, Nicholson RT,

et al.: International validation of a

dithiothreitol (DTT)-based method to

resolve the daratumumab interference

with blood compatibility testing.

Transfusion 2016; 56:2964–2972

11 Hosokawa M, Kashiwagi H, Nakayama

K, et al.: Distinct effects of daratu-

mumab on indirect and direct

antiglobulin tests: a new method

employing 0.01 mol/L dithiothreitol

for negating the daratumumab inter-

ference with preserving K antigenicity

(Osaka method). Transfusion 2018;

58:3003–3013

12 Lancman G, Arinsburg S, Jhang J,

et al.: Blood transfusion management

for patients treated with anti-CD38

monoclonal antibodies. Front Immunol

2018; 9:2616

13 Chari A, Arinsburg S, Jagannath S,

et al.: Blood transfusion management

and transfusion-related outcomes in

daratumumab-treated patients with

relapsed or refractory multiple mye-

loma. Clin Lymphoma Myeloma Leuk

2018; 18(1):44–51

14 Cushing MM, DeSimone RA, Goel R,

et al.: The impact of Daratumumab on

transfusion service costs. Transfusion

2019; 59(4):1252–1258

15 http://www.accessdata.fda.gov/drugsa

tfda_docs/label/2016/761036s004lbl.

pdf.

16 Fung MK, Eder AF, Spitalnik SL,

et al.: Technical manual, 19th edn.

Bethesda (MD), AABB, 2017

17 R Core Team: R: A language and envi-

ronment for statistical computing.

Vienna, Austria: R Foundation for Sta-

tistical Computing, 2018. [Available at

https://www.R-project.org/]

18 Valenzuela C: 2 solutions for estimat-

ing odds ratios with zeros. Rev Med

Chil 1993; 121:1441–4

19 Cid J, Lozano M, Fernandez-Aviles F,

et al.: Anti-D alloimmunization after

D-mismatched allogeneic hematopoi-

etic stem cell transplantation in

patients with hematologic diseases.

Transfusion 2006; 46:169-73

20 Boctor FN, Ali NM, Mohandas K,

et al.: Absence of D- alloimmunization

in AIDS patients receiving D-mis-

matched RBCs. Transfusion 2003;

43:173–6

21 Yuan S, Davis R, Lu Q, et al.: Low risk

of alloimmunization to the D antigen

in D- orthotopic liver transplant recip-

ients receiving D+ RBCs periopera-

tively. Transfusion 2008; 48:2653–5

22 Yazer MH, Triulzi DJ: Detection of

anti-D in D- recipients transfused with

D+ red blood cells. Transfusion 2007;

47:2197–201

23 Schuetz C, Hoenig M, Moshous D,

et al.: Daratumumab in life-threaten-

ing autoimmune hemolytic anemia

following hematopoietic stem cell

transplantation. Blood Adv 2018;

2:2550–2553

24 Chapuy CI, Kaufman RM, Alyea EP,

et al.: Daratumumab for Delayed Red-

Cell Engraftment after Allogeneic

Transplantation. N Engl J Med 2018;

379:1846–1850

25 Quach H, Benson S, Haysom H, et al.:

Considerations for pre-transfusion

immunohaematology testing in

patients receiving the anti-CD38 mon-

oclonal antibody daratumumab for the

treatment of multiple myeloma. Intern

Med J 2018; 48:210–220

26 van de Donk N, Richardson PG, Mala-

vasi F: CD38 antibodies in multiple

myeloma: back to the future. Blood

2018; 131:13–29

27 Velliquette RW, Aeschlimann J, Kir-

kegaard J, et al.: Monoclonal anti-

CD47 interference in red cell and

platelet testing. Transfusion 2019;

59:730–737

212 Z. Ye et al.

https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm530249.htm

http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf

https://www.R-project.org/

Copyright of Vox Sanguinis is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.