1. CD 10 positive: Follicular or Burkitt's
2. CD5 positive: CLL, Mantle cell [ FMC7, SOX11 positive in Mantle, neg CLL].
3. FMC7 positive: Mantle cell, Hairy cell
4. CD 23: positive in CLL
5. TDT positive: lymphoblastic lymphoma [ if CD 20+, then B cell, if CD 20 neg, then T cell]
Definition and complications in ABO-mismatched HSCT
Major ABO-mismatched HSCT
Major ABO-mismatched HSCT can cause hemolysis of donor’s erythrocytes by recipient’s IHAs10. In bone marrow derived grafts, hemolysis is more common than PBSC due to the high amount of erythrocytes in bone marrow11.
In major ABO-mismatched HSCT, hemolysis can be prevented by removing erythrocytes from graft. Insignificant hemolysis can also occur during erythrocyte engraftment due to destruction of erythrocytes containing donor’s antigens by means of recipient’s IHAs12. Finally, these reactions cause pure red cell aplasia (PRCA) in the majority of patients who had major ABO-mismatched HSCT 13. Antibody titers can be diminished in major ABO-mismatched HSCT by plasma or whole blood exchange before engraftment8.
Minor ABO-mismatched HSCT (passenger lymphocytes syndrome)
About 7-14 days after the infusion of graft, hemolysis occurs due to donor’s IHAs against recipient’s erythrocytes14.
1. This immediate hemolysis can be more severe than major ABO-mismatched HSCT that usually decreases after 5-10 days. In this situation, direct antiglobulin test (DAT) is usually positive against recipient’s erythrocytes antigens.
2. Passenger lymphocyte syndrome: A second hemolytic reaction occurs due to immunization of donor’s B lymphocytes, which is called passenger lymphocytes (PL) and production of IHAs against recipient’s erythrocytes, which is called “delayed hemolysis”. An important factor in development of PL syndrome is PBSC-derived grafts due to high lymphocyte content15.
In minor ABO-mismatched HSCT, IHAs can be removed from the graft by various techniques. There is a significant association between minor ABO-mismatched HSCT and increased risk of acute graft-versus-host disease (aGVHD) in patients.
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375375/
Pearls in Stem cell transplant for the boards
Reference ASH
Know the indications for :
1. Allo SCT
AML: CR1 for intermediate or poor risk, CR2 for favorable risk, primary refractory, MDS or t-AML
ALL: Ph+ in CR1, any relapse, failure to achieve MRD neg after first induction, in AYA if high risk features such as iAMP 21 ( intrachromosomal amplification of chromosome 21), B cell with poor risk, 11 q 23
MDS: Intermediate or high risk, transfusion dependence, refractory cytopenias, moderate or severe fibrosis, therapy associated, adverse cytogenetics
CML: T3151 mutation, refractory or intolerant, accelerated or blast crisis
MF- DIPSS 2 or higher, DIPSS1 with other poor risk features, transfusion dependence, possibly triple neg MF
CLL: Richter's, second or higher progression
2. Auto transplant
a. Multiple myeloma
b. Chemosensitive Relapsed Hodgkin and NHL
c. Mantle cell
d. Autoimmune disease
e. Relapsed germ cell
f. T cell lymphoma ( not supported by phase 3 trials, but done in practice as for Mantle cell)
TYPES of transplant and stem cell sources
Auto
Allo- sibling donor
Haplo identical ( alternative donor)
MUD 10/10
Cord blood ( alternative donor)
Syngeneic - identical twin ( do not use when you want GVL effect, e.g AML)
Why syngeneic is not used in AML: We want the GVL effect, and you do not get that with an identical twin.
Stem cell sources
a. Umbilical- low risk of GVHD, prolonged time to engraftment
b. bone marrow: inconvenient to donors, no difference in survival compared to peripheral blood, less GVHD compared to peripheral SCT
c. Peripheral blood: higher CD 34 and T lymphocytes, so faster engraftment but higher GVHD
Preference of donors:
First: sibling, then second would be fully matched unrelated
Third- haplo, cord
Finally unmatched unrelated
HLA matching is important
Gender Female donor to male recipient higher GVHD because Y chromosome acts as a minor antigen
Biggest risk for GVHD: HLA mismatch
Calcineurin associated TMA- stop the drug
Calcineurin associated PRES ( altered mentation) in the peri transplant period- stop the drug
Hepatic VOD- defibrotide
GVHD rx in steroid refractory
Acute- Jakafi
Chronic- Ibrutinib, Belumosidil
Idiopathic pneumonia syndrome- steroids, etanercept
