"Catch-Up Vaccinations Post-Stem Cell Transplant: A case series and review of the literature".

Introduction

Vaccination is a well-tolerated therapeutic intervention to prevent infections after any type of stem cell transplant [ 1 ]. Since all types of immunosuppressive therapy, including transplantation, are likely to suppress the response to vaccination, it might be fruitful to administer vaccines before the start of therapy for hematological malignancies or before stem cell transplant [ 2 ].

Vaccinating those specific populations could be challenging and difficult. An individualized immunization approach, modulating the inception and intensity of the vaccination schedule according to transplant characteristics, transplant-related complications, and immune recovery status, may improve vaccine efficacy in this specific population [ 3 ]. However, certain vaccines may be recommended, others should be avoided, like live vaccines, and still others may be used with no particular risk [ 2 ]. For the 2019 coronavirus disease (COVID-19), vaccination is considered one of the most promising and socioeconomically sustainable strategies to help control the pandemic, and several vaccines are currently distributed in nationwide mass immunization campaigns. Very limited data are available on the benefits and risks of COVID-19 vaccination in immunocompromised patients and, in particular, in autologous stem cell transplant recipients, as they were excluded from phase III trials. This case series summarizes current knowledge, international guidelines, and controversies regarding all types of vaccination in these vulnerable populations [ 4 ].

This case series describes patients who underwent Autologous Stem Cell Transplantation (ASCT) and were referred for post-transplant catch-up vaccination. This series summarize clinical practical considerations, current guidelines, and emerging challenges related to vaccination in this vulnerable population, highlighting areas where further research is needed. The evidence was often limited; there is still a great need for research on the exact vaccines needed for those patients after transplants, and areas that warrant future investigation are highlighted.

Case series

We present a series of three patients who were referred from King Abdulla Medical City (KAMC) Oncology center who underwent ASCT and received post-ASCT vaccinations. This series illustrates best practice regarding timing, intervals, vaccine selection, and follow-up, and highlights challenges that may be encountered in similar immunocompromised patients.

Case 1

A 16-year-old Saudi male with primary refractory stage IVB Hodgkin lymphoma (HL), initially diagnosed in June 2018 with pericardial effusion and multiple small pulmonary nodules (bone marrow negative), demonstrated significant lymph node regression and complete resolution of pulmonary nodules on interim computed tomography (CT) in October 2019. He completed frontline chemotherapy in December 2019; however, end-of-treatment CT in January 2020 revealed newly enlarged right supra- and infra-clavicular and subpectoral lymph nodes, with the largest measurin 1.2 × 0.8 cm. He subsequently received four cycles of IGEV (ifosfamide, gemcitabine, vinorelbine, prednisone) chemotherapy in Germany starting in March 2020, followed by BEAM (carmustine [BCNU], etoposide, cytarabine [Ara-C], melphalan) conditioning and ASCT on June 24, 2020, with a CD34+ cell dose of 10.7 × 10⁶ cells/kg. Follow-up CT imaging in January 2022 demonstrated complete response. He initiated post-ASCT catch-up vaccinations in March 2022 with no minor or major adverse effects being observed following vaccine administration, and post-vaccination serologic testing demonstrated an excellent response to the hepatitis B vaccine (HBV), with hepatitis B surface antibody (HBsAb) levels >1000 mIU/mL.

Case 2

A 25-year-old Bangladeshi male with Hodgkin lymphoma (HL) was diagnosed in 2017 with stage IIB unfavorable disease and treated with six cycles of ABVD (adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine) chemotherapy, followed by bilateral neck radiotherapy completed in June 2018. He relapsed in November 2020 with intra-abdominal lymphadenopathy and negative bone marrow involvement and received six cycles of GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy with disease progression. He subsequently achieved complete metabolic response after two cycles of nivolumab and brentuximab. He underwent BEAM (carmustine [BCNU], etoposide, cytarabine [Ara-C], and melphalan) conditioning followed by ASCT in September 2021, complicated by mucositis and febrile neutropenia, and received 11 cycles of post-transplant brentuximab consolidation before discontinuation due to neuropathy and drug unavailability. Following ASCT, the patient received post-transplant catch-up vaccinations, including pneumococcal conjugate (PCV-13), pneumococcal polysaccharide (PPSV-23), influenza, and coronavirus disease 2019 (COVID-19) vaccines, with vaccination timing coordinated to account for the potential impact of post-ASCT maintenance therapy on immune response. Post-vaccination serologic testing demonstrated a protective response to the hepatitis B vaccine, with HBsAb level of 47 mIU/mL. Imaging demonstrated complete remission through May 2024; however, positron emission tomography (PET) in October 2024 revealed new bilateral axillary lymphadenopathy (Deauville score 4), concerning disease recurrence.

Case 3

A 52-year-old Egyptian male was diagnosed with IgA Kappa multiple myeloma on March 18, 2024. At diagnosis, PET-CT showed disseminated lytic lesions, and bone marrow biopsy revealed 16% plasma cells. He completed 24 weeks of VCD (bortezomib, cyclophosphamide, dexamethasone) chemotherapy by December 29, 2024, followed by ASCT on February 19, 2025. In October 2025, health education about the required vaccines was given to the patient and Post-ASCT vaccinations were initiated with first doses of hepatitis B vaccine, PCV-13 vaccine, and influenza vaccine administered on October 15, 2025. Nine days later, he presented to the emergency room with fever, throat pain, mild dry cough, and mild muscular chest discomfort; he denied dyspnea or other systemic symptoms. On examination, he was well-appearing, alert, vitally stable, with clear lungs, normal heart sounds, a soft, non-tender abdomen, and no extremity abnormalities. ECG was normal. Initial management included symptomatic treatment, laboratory investigations, troponin measurement, and chest X-ray. Hematology recommended a full septic screen, antibiotics if indicated, and supportive care including hydration, antipyretics, and antiemetics. On reassessment, he was asymptomatic and vitally stable and was discharged home with medications explained, and instructions to return if symptoms recurred. A hematology/oncology outpatient follow-up appointment was scheduled. The PCV-13 vaccine was administered on 15–10–2025, followed by the PPSV-23 vaccine on 17–12–2025, with an interval of approximately 8 weeks between the two vaccines. The influenza vaccine was given in two doses on 15–10–2025 and 12–11–2025 due to the absence of any prior influenza vaccination history, maintaining an interval of about 4 weeks between doses. HBV vaccine series was initiated with the first dose on 15–10–2025 and the second dose on 16–11–2026, and the patient is scheduled for a follow-up visit at the end of January 2026 to complete the remaining vaccinations.

Discussion

A five-time increase in ASCT survivors is expected in the United States between 2009 and 2030 [ 2 ]. Patients with hematologic malignancy often have a history of chemotherapy or ASCT which makes the recovery of the number and function of peripheral blood lymphocytes relatively slow and they are considered severely immunocompromised (high risk) of morbidity and mortality from certain vaccine-preventable diseases, such as influenza, pneumococcal disease and COVID-19 infection [ 1 , 3 , 4 ]. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommends certain vaccines for routine use in all persons, stratified by age and clinical indication [ 1 ].

This case series report demonstrates an updated catch-up vaccine schedule based on the last international recommendations for the immunocompromised patient at KAMC Oncology Center, one had a history of IGEV salvage chemotherapy followed by ASCT in June 2022 and received salvage chemotherapy that was used to decrease tumor size followed by high-dose chemotherapy and SCT (infusion of immature blood cells). The catch-up vaccination schedule aims to provide optimal protection against vaccine-preventable diseases as soon as possible by completing the recommended vaccination with minimum intervals. Follow-up of this patient showed complete response. In the second patient, he was diagnosed with HL and treated with a combination of chemotherapy and radiotherapy and showed relapse; accordingly treated with chemotherapy and demonstrated response after two cycles of nivolumab and brentuximab. Then, he underwent BEAM conditioning regimen followed by ASCT; following ASCT, he received post-transplant catch-up vaccinations, including PCV-13, PPSV-23, influenza, and COVID-19 vaccines, with scheduling coordinated to consider the potential impact of post-ASCT maintenance therapy on immune response and imaging showed complete remission. Last case was diagnosed with IgA Kappa multiple myeloma and treated with chemotherapy followed by ASCT. He started post-ASCT vaccinations received first doses of hepatitis B vaccine, PCV-13 vaccine, and influenza vaccine. He is currently under hematology/oncology follow-up.

Vaccination is an important intervention to prevent many communicable diseases especially for immunocompromised patients [ 3 ]. Several studies have shown that ASCT recipients also lose protective immunity during long-term follow-up will influence the responses to vaccination especially during the first 6 months after transplantation [ 5 ].

Nivolumab, a PD-1–blocking IgG4 monoclonal antibody, enhances T-cell activation by releasing immune checkpoint–mediated inhibition. In the post–stem cell transplantation setting, where immune reconstitution and tolerance are still developing, PD-1 blockade may lead to exaggerated or dysregulated responses to vaccine antigens, with potential implications for vaccine safety and efficacy, including immune-mediated toxicity or graft-versus-host disease. These considerations underscore the importance of careful timing of vaccination in patients previously exposed to nivolumab [ 6 ].

Three central societies and unanimity groups have published guidelines for stem cell transplant recipients: the American Society of Blood and Bone Marrow Transplantation (ASBMT) and the European Group of Blood and Marrow Transplantation (EBMT). These recommendations, connected with ACIP recommendations and newly available published data, serve as the basis of this report [ 5 , 7 ].

Types of vaccine and timing

Regardless of prior vaccination history, inactivated (killed) vaccines—which are ideally protein- or polysaccharide-based—are recommended. Polysaccharide vaccines are generally less immunogenic; however, conjugation with protein carriers enhances the immune response. Zoster vaccines contain genetically engineered antigens and are typically inactivated [ 8 ].In contrast, live attenuated vaccines (LAVs), such as the measles, mumps, and rubella (MMR) vaccine and the varicella vaccine, contain weakened but replication-competent organisms. Patients who have undergone SCT or ASCT should not receive LAVs until at least 24 months post-transplant, and only if laboratory testing does not document immunity [ 5 , 8 ]. Vaccination should generally be administered >6 months after transplant; with a minimum interval of 4 months post-ASCT [ 7 ].

According to the CDC and the Advisory Committee on Immunization Practices (ACIP), antibody titers to vaccine‑preventable diseases—including tetanus, poliovirus, measles, mumps, rubella, and encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type b—can decline significantly within 1 to 4 years after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT) if recipients are not revaccinated. Therefore, routine post-transplant revaccination is recommended for all SCT recipients, with timing and vaccine choice tailored to immune recovery and transplant type [ [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] ].

Inactivated-Killed-Vaccines

Influenza vaccine

Many observational reports propose a decrease in the risk of lower respiratory tract infection and hospitalization among vaccinated ASCT patients. There is consensus across existing guidelines recommending seasonal influenza vaccination; the key recommendations, regardless of transplant type, are [ 7 ]:

Administer > 6 months after transplant but may begin at 4 months if influenza season has begun.

If the inactivated influenza vaccine is not given before, two doses should be given 4 weeks apart in the first year after transplant.

One dose should be given every year after that.

Td (Tetanus and Diphtheria) or DTaP (Diphtheria, Tetanus, and a Cellular Pertussis

Three doses of tetanus- and diphtheria-containing vaccine should be administered six months following ASCT. ➢ For patients<7 years of age, three doses of DTaP vaccine may be administered. ➢ For patients ≥7 years of age, administration of three doses of DTaP vaccine may be given. ➢ Alternatively, a dose of Tdap vaccine should be administered, followed by two doses of Td.

PCV13 (pneumococcal conjugate vaccine) and PPSV23 (polysaccharide pneumococcal vaccine)

Sequential administration of three doses of PCV13 is recommended, beginning 3–6 months after the transplant, followed by a dose of PPSV23 [ 10 ].

Other sources support three doses of PCV13 at 4-week intervals, with a dose of PPSV23 recommended 8 weeks after the last dose of PCV13 and 12 months after the transplant [ 11 ].

Meningococcal serogroups A, C, W, and Y vaccine (MenACWY)

The target ASCT patients for meningococcal vaccination are similar to those in the general population

Special situations for MenACWY-y Anatomical or functional asplenia (including sickle cell disease), HIV infection, persistent complement component deficiency, complement inhibitors (e.g., eculizumab), a two-dose series of MenACWY-D (Menactra, Menveo, or MenQuadfi) at least 8 weeks interval.

Booster dose is every 5 years after completion of the primary schedule [ 12 ].

Hep B vaccine (HepB)

Three-dose series of hepatitis B vaccine at 0, 1, and 6 months [minimum intervals as following: ✓ Dose 1 to dose 2: 4 weeks ✓ Dose 2 to dose 3: 8 weeks ✓ Dose 1 to dose 3: 16 weeks

Post-vaccine serologic testing is recommended to assess the response to hepatitis B vaccination 1–2 months following the third dose.

A second three-dose series is recommended in nonresponders (ie, those with anti-HB concentrations <10 milli-international units [mIU]/mL) [ 11 ].

Hepatitis A vaccine (HepA)

Hep A vaccine is indicated for patients at risk such as patients living or travelling to endemic areas

Patients with chronic liver disease may benefit from Hep A vaccine

If indicated, a two-dose series with a minimum interval of 6 months [ 13 ].

Haemophilus influenza type-B vaccine (Hib)

Three-dose series 4 weeks apart starting 6–12 months after transplant regardless of Hib vaccination history [ 5 ].

COVID-19 vaccine

The COVID-19 vaccination is recommended for everyone aged 12 years and older for the prevention of coronavirus disease 2019 (COVID-19)

Updated considerations for the use of an additional mRNA COVID-19 vaccine dose after an initial 2-dose COVID-19 mRNA vaccine series for immunocompromised people

Studies have further demonstrated that including an additional mRNA COVID-19 vaccine dose after an initial 2-dose primary mRNA COVID-19 vaccine series in some immunocompromised populations may enhance the immune response.

The additional dose should be administered at least 28 days after the completion of the initial mRNA COVID-19 vaccine series. Currently, the CDC is recommending that moderately to severely immunocompromised people receive an additional dose [ 8 ].

Live Attenuated vaccine

For live vaccines, (MMR and Varicella) safe interval of 24 months must pass from the transplantation.

Measles, Mumps, Rubella vaccine (MMR)

The serology must be checked after ASCT in: ✓ Pediatrics patients ✓ Adult patients who received the MMR vaccine during immunosuppressed or 6 to 8 weeks before the initiation of immunosuppression ✓ Women who may become pregnant [ 11 ]

A 2-dose series of the MMR vaccine with a minimum interval of 4 weeks (28 days) must be administered to all ASCT recipients who are seronegative and meet all the following criteria: ✓ A safe interval after transplant (24 months) has passed since transplantation ✓ The recipient does not have active GVHD ✓ The recipient is not receiving any immunosuppression therapy ✓ The last dose of intravenous immunoglobulin (IVIG) was administered >8 to 11 months ago [ 11 ]

Varicella vaccine

A 2-dose series of the Varicella vaccine with a minimum interval of 4 weeks (28 days) must be administered to all ASCT recipients who are seronegative and meet all the following criteria: ✓ A safe interval after transplant (24 months) has passed since transplantation ✓ The recipient does not have active GVHD ✓ The recipient is not receiving any immunosuppression therapy ✓ The last dose of intravenous immunoglobulin (IVIG) was administered >8 to 11 months ago [ 11 ]

Zoster vaccines

Vaccination against herpes zoster (shingles) in ASCT recipients is highly recommended

The recombinant zoster vaccine (RZV) is for ≥18 years patients.

2-dose vaccine series at least two months apart [ 9 ].

The live attenuated zoster vaccine (ZVL) is not recommended.

Table (1) illustrates thecatch-up vaccination schedule post-stem cell transplant.

Vaccination Documentation

The administered vaccines are registered in the National Vaccination Registry (NVR) through the SEHA Platform, an electronic system developed by the Saudi Ministry of Health to maintain official vaccination records. Once the vaccination is documented, an official vaccination certificate becomes immediately available to the patient through the mobile application Sehhaty. The certificate includes detailed information such as the vaccine type, number of doses administered, batch number, vaccination date, and the name of the healthcare facility providing the vaccination. Patients can easily access their vaccination history through the Sehhaty application and download the vaccination certificate as a PDF report for personal records or official purposes.

Vaccination in the scenarios of post-transplant maintenance therapy

An increasingly common clinical scenario following SCT or ASCT is the use of maintenance therapies, including monoclonal antibodies such as rituximab. These agents may impair humoral immune responses, potentially reducing vaccine immunogenicity, particularly for B-cell–dependent vaccines. Nevertheless, current guidelines recommend proceeding with prioritized inactivated vaccines, including pneumococcal conjugate vaccines (PCV-13 or PCV-20) followed by the pneumococcal polysaccharide vaccine (PPSV-23), as well as annual inactivated influenza vaccination. Whenever feasible, vaccines should be administered at least 4 weeks before initiating B-cell–depleting therapy, or delayed until approximately 6 months after the last dose to maximize immune response. Live attenuated vaccines remain contraindicated in patients receiving ongoing immunosuppressive or biologic therapy. Given the limited available data, vaccination strategies in patients receiving post-SCT maintenance therapy should be individualized, balancing infection risk, timing of therapy, and anticipated immune recovery [ 14 ].

Conclusion

The post-transplant patients are at increased risk of acquiring vaccine-preventable diseases. Implementation of an updated catch-up vaccines schedule with a minimum interval between vaccine doses, based on evidence, resulted in higher immunization rates. Where possible, vaccinations should be given before transplant. In addition, vaccination in the increasingly common scenario of patients receiving post autologous transplant maintenance therapies (i.e. daratumumab, rituximab, brentuximab) is recommended.

Availability of data and materials

The entirety of the data has been encapsulated within the manuscript and supplementary files.

Funding

This research did not receive any financial backing or support from any source.

Ethics approval and consent to participate

Ethical approval was taken from the Institutional Review Board (IRB) in KAMC, Makkah Al-Mukarramah, Saudi Arabia. The author attests to having obtained all relevant informed consent documentation from the patients. All patients provided explicit consent for the disclosure of their clinical information in this manuscript, with full comprehension that their identities shall remain anonymous.

Informed consent statement

Ethical approval was obtained from the Institutional Review Board. Written informed consent was obtained from the patients. All necessary consents, permissions, and releases were secured before starting the study. No personal or identifying information such as names, initials, hospital or social security numbers, or dates of birth were included. All efforts were made to ensure the privacy and confidentiality of the patient and research subjects.

CRediT authorship contribution statement

Rehab Mohammed Gaafar: Writing – review & editing, Writing – original draft, Methodology. Afnan Mohsen Alamodi: Visualization, Resources, Data curation.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

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Associated Data

Data Availability Statement

The entirety of the data has been encapsulated within the manuscript and supplementary files.