14.2 Hematological and Immunological Effects

TCO IV.A.10–11 tests hematologic and immunologic acute, chronic, and late effects of myelosuppressive chemotherapy, immunotherapy, and HSCT. This is not the sepsis, disseminated intravascular coagulation, or transfusion-reaction emergency chapter. Those playbooks live later. Here the nurse times the nadir, teaches fever as a same-day call, keeps Pneumocystis jirovecii pneumonia (PJP) prophylaxis on the calendar, and names immune reconstitution, hypogammaglobulinemia, and therapy-related myeloid neoplasm as late maps.

A 4-year-old on ALL delayed intensification whose absolute neutrophil count (ANC) is 80/µL on day 10, a teenager with acute myeloid leukemia (AML) on antifungal prophylaxis, and a 9-year-old day +180 after allogeneic HSCT whose school wants every vaccine this Friday are the pictures.

Myelosuppression, ANC, and fever teaching

Almost every cytotoxic pathway injures marrow. Neutropenia, anemia, and thrombocytopenia follow a nadir—commonly about 7 to 14 days after many multiagent cycles, longer after some agents (for example, nitrosoureas). Do not treat one printed day as the only ONCC clock; know the protocol’s expected window and teach families when counts will likely bottom.

ANC is neutrophils available to fight bacteria (classically white-cell count × percent neutrophils and bands). Severe neutropenia is often an ANC under 500/µL. Fever during that window is fever and neutropenia, a medical emergency signposted to the sepsis chapter. The IV.A job is teaching before the nadir: measure temperature as the team instructs, call at the protocol fever threshold (centers differ; do not invent a single ONCC number), do not give acetaminophen or ibuprofen at home to see if it breaks before calling, and do not wait three days because the child looks well. Clinic on a Friday before a known nadir includes the after-hours number in the caregiver’s phone.

Colony-stimulating factors such as filgrastim appear as ordered; the dedicated supportive-care section owns dosing. Here, know that growth factors do not replace fever teaching. Platelet and hemoglobin nadirs travel with the neutrophil curve; bleeding precautions and transfusion thresholds belong with the blood-product chapter, but families still need to hear that bruising and pallor cluster in the same week as the fever risk.

PJP, fungal prophylaxis, and viral reactivation

PJP (also called PCP) is preventable. Trimethoprim-sulfamethoxazole is the first-line prophylaxis on ALL, other intensive lymphoma pathways, and HSCT timelines. Missed doses are how children present with subacute dyspnea and hypoxia. If the child cannot take trimethoprim-sulfamethoxazole (allergy, delayed methotrexate clearance on some days), the team chooses pentamidine, dapsone, or atovaquone—not skip it this month. Hold rules around high-dose methotrexate are protocol-specific; restart prophylaxis when the protocol says.

Fungal prophylaxis is expected on AML induction and consolidation and on HSCT pathways (and other prolonged severe neutropenia). Agents are protocol-specific (fluconazole, mold-active azoles such as posaconazole or voriconazole, or an echinocandin). Do not invent one national drug as ONCC fact. Teach families that a new fever on AML therapy is still an infection workup, not proof the azole failed so they can stop it.

Viral reactivation tracks prior infection and T-cell immunity:

• Herpes simplex virus (HSV): oral or cutaneous recrudescence during neutropenia or HSCT; acyclovir prophylaxis is common around transplant.
• Varicella-zoster virus (VZV): childhood chickenpox becomes zoster (shingles) under immunosuppression; report a dermatomal vesicular rash the same day.
• Cytomegalovirus (CMV): especially after allogeneic HSCT; programs use blood PCR surveillance and preemptive therapy. A little fever after day +30 is not automatically a virus you ignore.
• Hepatitis B virus (HBV) with rituximab (anti-CD20) and other B-cell–depleting therapy: screen HBsAg and anti-HBc before rituximab; antiviral prophylaxis as infectious disease orders. HBV reactivation can be fulminant. Do not hang rituximab on an unscreened teenager.

Transfusion dependence and alloimmunization

Some children become transfusion dependent: repeated red-cell or platelet support through intensive blocks, marrow failure, or post-HSCT poor graft function. Every exposure risks alloimmunization—HLA antibodies that make platelets refractory, or red-cell antibodies that delay crossmatch. Use leukoreduced products as standard pediatric oncology practice to reduce HLA alloimmunization and CMV risk; irradiated products when the protocol requires them to prevent transfusion-associated graft-versus-host disease. Notify the blood bank early when a child is a known alloimmunized or chronically transfused patient. Iron overload is a late companion of chronic red-cell transfusion; chelation belongs with hematology, not as an invented ferritin cutoff here.

Do not complete a unit that is causing a reaction in order to finish the volume. Reaction algorithms are the transfusion-emergency and blood-product chapters.

Immune reconstitution, live vaccines, hypogammaglobulinemia, and secondary MDS/AML

After allogeneic HSCT, innate recovery (neutrophils) is not the same as adaptive immune reconstitution. B- and T-cell recovery takes months to years and is slower with chronic GVHD and ongoing immunosuppression. Revaccination schedules are protocol-specific. The CPHON teaching sentence is: live vaccines (measles-mumps-rubella, varicella, live attenuated nasal influenza, oral rotavirus) wait until immune recovery per the transplant team. A school clinic that wants to give measles-mumps-rubella on day +90 because everyone is due is not the authority. Inactivated vaccines restart on the transplant program’s calendar, not on a parent’s phone reminder from the pre-transplant pediatrician.

Rituximab and CD19 chimeric antigen receptor T-cell (CAR-T) therapy can produce prolonged B-cell aplasia and hypogammaglobulinemia. Recurrent sinopulmonary infections and very low IgG are the clues. Intravenous immunoglobulin (IVIG) replacement is given as ordered. This is immune failure, not ordinary winter viruses. Do not send that child through a live-vaccine school clinic either.

Secondary myelodysplastic syndrome (MDS) and secondary AML are late therapy-related myeloid neoplasms after alkylators, etoposide (a topoisomerase II inhibitor), and radiation. Alkylator-related disease tends to appear later; etoposide-related disease often appears earlier and may be KMT2A-rearranged. Teach the concept and the need for a new cytopenia workup years later. Do not invent an incidence percentage or a guaranteed year of onset as ONCC fact. The chemotherapy chapter names the same etoposide risk; this section is the survivorship cytopenia that must not be filed as normal recovery.

The CPHON product is a family that calls at the first protocol fever, a trimethoprim-sulfamethoxazole calendar that was not quietly dropped, an AML patient who actually takes fungal prophylaxis, a transplant clinic that—not the school nurse—clears live vaccines, and a survivorship note that names alkylators and etoposide without a made-up secondary-leukemia percentage.