Late complications:

Relapse of disease after HSCT:

• Diagnosis of relapse must be made very carefully, as
  • Residual radiographic abnormalities remain even after treatment of lymphoma
  • Reduction of paraproteins takes several months in myeloma patients
  • Following “Reduced intensity conditioning” complete tumor eradication occurs after months.
  • PCRs are positive even beyond 3 years of HSCT without having any risk of relapse.
• Strategies to decrease risk of relapse
  • Autologous SCT
    • Radiation to prior sites of bulky disease
    • Immunological interventions to generate “autologous graft versus tumor response”- IL2, vaccination with idiotype pulsed dendritic cells.
    • Allogenic NK cell infusion
    • Use of monoclonal antibodies such as Rituximab
  • Allogenic SCT
    • Mismatching for Killer cell immunoglobulin like receptor (KIR) ligands
• Treatment:
  • Relapse following Auto SCT:
    • Salvage therapy with chemotherapy +/- radiation followed by allogenic SCT
  • Relapse following Allo SCT:
    • Palliation
    • Second myeloablative SCT
    • Donor lymphocyte infusion (Has high risk of severe GVHD and marrow aplasia)- “Awakens” endogenous graft versus leukaemia effector cells.

Chimerism and minimal residual disease monitoring after HSCT:

• MRD assessment is usually done using PCR. Fusion transcripts and Ig/TCR gene rearrangements are usually used as targets.
• Chimerism is the ratio of donor and recipient derived cells. 
• Uses of chimerism monitoring
  • Permits the assessment of immunological interactions between donor and recipient
  • Provides information for pre-emptive therapeutic interventions
  • Enables the assessment of successful engraftment
  • Early identification of graft rejection
• Methods of chimerism assessment
  • In case of sex mismatched transplants- FISH analysis of X and Y chromosomes
  • In case of same sex transplants- PCR for DNA microsatellites- short tandem repeats (Variable nucleotide tandem repeats-VNTR). For this pretransplant samples of donor and recipient are necessary. Heterozygous markers are used for chimerism monitoring.

Things to do during annual follow up of transplant patients:

• History, examination and counselling
  • Smoking and tobacco avoidance
  • Blood pressure
  • Ocular and fundus examination
  • Cancer screening  and education
  • Psychological screen and assessment of quality of life
• Investigations
  • LFT
  • Creatinine
  • Gonadal function in pre-pubertal women
  • TFT (If neck is irradiated)
  • Pap smear
  • Mammography (Women older than 40 years)
  • Chimerism study
  • MRD assessment (for up to 5 years)

Post transplant vaccination (Allogeneic and Autologous transplant):

• Start 1 month after stopping  immunosuppression and only if there are no signs of GVHD
• When multiple doses are necessary, unless advised otherwise, they have to be given 1 month apart
• Patients have to be continued on oral penicillin till 1 year after starting vaccination

• Optional vaccines include: Hepatitis A, Varicella, Human papilloma virus, yellow fever, rabies, tick borne encephalitis, Japanese encephalitis.
• BCG, Live oral polio, Intranasal influenza, oral live typhoid, intramuscular typhoid and cholera are contraindicated in post BMT patients.
• Family members, close contacts and health care workers must be vaccinated against
  • Hepatitis A
  • Annual influenza vaccine
  • Rota virus
  • MMR
  • Pertussis
  • Varicella (For >12 years old)