We read the recent article on Rituximab by Borker, et al. with
great interest [1]. This letter reports our experience with Rituximab in
children for various indications. A brief tabulation of Rituximab usage
in eleven children admitted in our unit from 2006 to 2011 is presented
in Table I. We have previously reported 5 of these 11
patients [2]. Rituximab has good efficacy but some severe side-effects
which we highlight in this report.
TABLE I Details of Rituximab Usage in Children for Various Indications
Indication |
Age/ sex |
Dosage/Schedule |
Response |
Side effects |
Replacement
IVIG |
Outcome |
|
|
|
|
|
|
|
AIHA |
1 yr/ M |
Std.D × 4 wks + Cy × 8 doses |
DCT negative Transfusion free |
Not significant |
Yes |
Alive |
AIHA with HO-1 def |
11yr/F |
Std.D × 3 wks + Cy × 2 doses
Pred/ |
No response |
Not significant |
No |
Died (primary disease) |
Hemophilia-A with inhibitors |
13 yr/ M |
Std.D × 4 wks + Cy × 2 doses |
Inhibitors negative at 3
months |
Not significant |
No |
Alive |
FHLH with EBV-PTLD |
1½ yr/ F |
Std.D × 4 wks + Pred for GVHD |
PTLD subsided |
Not significant |
Yes |
Alive |
DLBCL |
16 yr/ F |
375 mg/m2 with each cycle of
R-CHOP × 2 cycles |
Partial Response |
Not significant |
No |
Alive |
Burkitt’s lymphoma |
5yr/M |
Std.D/ MPC842 chemo cycle × 4 |
CR |
Not significant |
No |
Alive |
ALL with ITP |
3yr/M |
Std.D x 4 wks |
Sustained rise in plts |
Diss. TB (responded to ATT) |
Yes |
Alive |
Chronic ITP |
10yr/F |
Std.D x 4 wks + CSA/Pred |
Sustained rise in plts |
CNS white matter changes |
No |
Alive with PML |
|
|
|
|
|
|
|
Chronic ITP |
7yr/M |
Std.D x 4 wks |
Sustained rise in plts |
Not significant |
No |
Alive |
Chronic ITP |
8yr/M |
Std.D x 4 wks |
Plts raised for 6-8
months then decreased |
Not significant |
No |
Alive |
Chronic ITP |
8 yr/ F |
Std.D x 4 wks +Aza |
Plts increased |
CMV infection |
Yes |
Died (CMV pneumonitis)
|
AIHA- Auto-immune
hemolytic anemia; ALL- Acute lymphoblastic leukemia; ATT-
Anti-tubercular therapy; Aza- Azathioprine; CMV-
Cytomegalovirus; CNS- Central nervous system; CSA- Cyclosporin-A;
Cy- Cyclophosphamide; DCT- Direct Coombs’ test; Diss.-
Disseminated; DLBCL- Diffuse large B-cell lymphoma; EBV-
Epstein-Barr virus; FHLH- Familial hemophagocytic
lymphohistiocytosis; GVHD- Graft versus host disease; HO-1- Heme
oxygenase-1; ITP- Immune thrombocytopenic purpura; IVIG-
Intravenous immunoglobulin; PML- Progressive multifocal
leukoencephalopathy; Pred.- Prednisolone; Plts- Platelets;
R-CHOP- Rituximab with CHOP chemotherapy; Std. D.- Standard dose
of Rituximab (375 mg/m2/wk); TB- Tuberculosis. |
We report 2 cases of autoimmune hemolytic anemia
(AIHA), the first being an infant refractory to steroid and intravenous
immunoglobulin (IVIG) who is now transfusion independent at 6 months
post-therapy with Rituximab and cyclophosphamide. The second patient who
presented with AIHA, nephritis, inflammation and asplenia did not
respond to Rituximab. She died of her disorder which was later diagnosed
as only the second reported case of human heme-oxygenase-1 deficiency
[3].
Rituximab based immune tolerance induction (ITI) in
the case of Hemophilia-A with inhibitors (high responder) succeeded in
clearing inhibitors 3 months post-ITI.
Of the 3 cases associated with lympho-proliferative
disorders, the first was a girl with Epstein-Barr virus induced
post-transplant lympho-proliferative disorder (PTLD)
post-matched-sibling donor stem-cell transplant for Familial
Hemophagocytic Lympho-histiocytosis. Rituximab produced a dramatic
improvement in her PTLD. The two cases of mature B-cell Lymphoma
responded well to chemotherapy combined with Rituximab.
The child with acute lymphoblastic leukemia with
refractory immune thrombocytopenic purpura (ITP) (one of 5 children with
ITP) maintained platelet counts >100,000/µL following Rituximab therapy.
The disseminated tuberculosis which he developed at the end of treatment
could be partly attributed to Rituximab-associated CD20+ cell depletion.
The four other cases of ITP non-responsive to IVIG,
Intravenous anti-D, steroids and cyclosporine received Rituximab and all
responded with an increase in platelets >l00,000/mm 3.
Three patients sustained their response but two of them developed
Rituximab therapy associated infectious complications (Table I).
The fourth showed a decline in platelet count after a transient increase
for about eight months.
As this data illustrates, Rituximab has wide and
effective applications in pediatric haematology-oncology. However,
adequate caution is warranted to pre-empt and institute early therapy,
if required, for opportunistic infections which may arise due to
resultant immunosuppression. Also, progressive multifocal
leukoencephalopathy (PML) is a rare but real complication of Rituximab
use and close clinical observation is essential [4].
References
1. Borker A, Choudhary N. Rituximab- Drug review.
Indian Pediatr. 2011;48:627-32.
2. Yadav SP, Misra R, Kharya G, Sharma SD, Sachdeva
A. Rituximab use in children - A single center experience. Blood.
2006;108:3892.
3. Radhakrishnan N, Yadav SP, Sachdeva A, Pruthi PK,
Sawhney S, Piplani T, et al. Human heme oxygenase-1 deficiency
presenting with hemolysis, nephritis, and asplenia. J Pediatr Hematol
Oncol. 2011;33:74-8.
4. Carson KR, Evens AM, Richey EA, Habermann TM,
Focosi D, Seymour JF, et al. Progressive multifocal
leukoencephalopathy after rituximab therapy in HIV negative patients: a
report of 57 cases from the Research on Adverse Drug Events and Reports
project. Blood. 2009;113:4834-40.
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