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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 5  |  Page : 54-58

Management of hematological malignancies during the COVID-19 pandemic


1 Department of Medical Oncology, S.L. Raheja (Fortis) Hospital and HCG Hospital, Mumbai, Maharashtra, India
2 Department of Pediatrics, Mumbai and Aarya Clinic, Sterling Hospital, Mumbai, Maharashtra, India

Date of Submission05-Apr-2020
Date of Decision06-Apr-2020
Date of Acceptance08-Apr-2020
Date of Web Publication25-Apr-2020

Correspondence Address:
Ashay Karpe
Aarya Clinic, Shop No 1, Ganjawala CHS, Near Pai Nagar Garden, Off SVP Road, Borivali (West), Mumbai - 400 092, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_123_20

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  Abstract 


Coronavirus disease 2019 (COVID-19) caused by novel coronavirus, which is structurally related to the virus causing severe acute respiratory syndrome, has emerged as a global health problem. During this pandemic, treatment of oncology patients especially patients with hematological malignancies has many challenges. In the absence of definite guidelines for the management of hematological cancers, we should follow certain principles for better treatment delivery with precautions to prevent COVID-19 infection in this vulnerable population with the least compromise in patient outcome

Keywords: Coronavirus disease 2019, leukemia, lymphoma, myeloma, treatment, COVID, SARS-CoV-2, India


How to cite this article:
Karpe A, Nagvekar-Karpe S. Management of hematological malignancies during the COVID-19 pandemic. Cancer Res Stat Treat 2020;3, Suppl S1:54-8

How to cite this URL:
Karpe A, Nagvekar-Karpe S. Management of hematological malignancies during the COVID-19 pandemic. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Nov 30];3, Suppl S1:54-8. Available from: https://www.crstonline.com/text.asp?2020/3/5/54/283293




  Introduction Top


Coronavirus disease 2019 (COVID-19) which predominantly affects the respiratory system has emerged as a global health problem.[1],[2] Studies have revealed that novel coronavirus is structurally related to the virus causing severe acute respiratory syndrome. The COVID-19 pandemic is a serious threat to public health and the health-care personnel.

Patients diagnosed to have malignancies usually have impaired immunity as compared to the general population, especially those affected with hematological malignancies. Chemotherapy regimens used in hematological malignancies are more likely to cause neutropenia, as compared to those given for solid tumors.[3] In many instances, these adverse effects/toxicities warrant hospitalization, where patients are vulnerable to various infections.

During the current COVID pandemic, which is highly infectious, continuing chemotherapy involves many challenges, as patients with hematological malignancies are at higher risk of getting opportunistic infections and can have a dismal outcome owing to low immunity.

All due precautions are to be followed for indoor as well as outdoor patients for screening, prevention, and treatment of COVID-19 as in the general population. Cancer patients who get infected with COVID-19 have to be managed as other patients, based on their own merit as per guidelines. In this article, we will be reviewing the optimal management of hematological cancers during the present health crisis.

We cannot have clear guidelines about the management of hematological malignancies during this pandemic. We must be able to deliver prompt treatment without much compromise in cancer outcomes for which we should follow certain principles when treating oncology patients to avoid exposure to probable or proven COVID-19 cases.

  1. Identifying patients as curative versus palliative
  2. Reducing the number of hospital visits for treatment (possibility of using telemedicine or video conferencing[4])
  3. Avoiding unnecessary hospital admissions
  4. Modifying the treatment intensity or supportive care (granulocyte colony-stimulating factor [GCSF] support, if indicated) to minimize the possibility of neutropenia[5] and infective complications
  5. In most cases, it is wiser to use escalation policy (start with a lower effective dose and then increase the dose as per tolerance) rather than de-escalation (starting with a higher dose and reducing the dose based on the toxicities) in select population, including older patients, patients with a borderline performance status, multiple comorbidities, and organ dysfunction
  6. Intensive treatments must be carried out in institutions where separate facilities are available for treatment of oncology patients as well as for management of complications (like febrile neutropenia). These facilities (outpatient department [OPD] or inpatient department) should not be overlapping with hospital sections where suspected or proven COVID-19 cases are screened or treated
  7. When treating these patients with chemotherapy, we also have to consider that traveling for treatment as well as for complications arising due to therapies can be difficult in the present scenario. In case of certain toxicities (like febrile neutropenia), if the patient is unable to reach the hospital, it can have a detrimental outcome[6]
  8. Another concern during treatment of acute leukemias, intensive chemotherapy in high-grade lymphomas, and stem cell transplant is the availability of blood products. Due to travel restrictions during the pandemic and unavailability of voluntary donors, many blood banks and hospitals are facing a paucity of blood products. We should have institutional blood product transfusion policies to optimize the use of blood products.


The following points can be considered when treating individual hematological malignancies, though not as guidelines or recommendations.

Lymphoma

Hodgkin's lymphoma

  1. Hodgkin's lymphoma is one of the most chemosensitive malignancies with improved survival[7]
  2. Patients fit for intensive chemotherapy regimens should be counseled about the potential risks in the present pandemic
  3. Thorough evaluation of the respiratory system prior to starting therapy must be done (especially as bleomycin, which can cause lung toxicity, is part of standard chemotherapy regimen, ABVD, consisting of doxorubicin, bleomycin, vinblastine, and dexamethasone)
  4. In patients who have a history of prior lung disease, alternative regimens containing etoposide,[8] instead of bleomycin, can be considered with GCSF support to avoid neutropenia. In affording patients, brentuximab vedotin[9] can be considered
  5. In case of relapsed refractory cases with borderline Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2) or uncontrolled comorbidities or compromised organ function, rather than intensive chemotherapy, oral chemotherapy protocols such as DECC[10],[11] (lomustine [CCNU], etoposide, chlorambucil, and dexamethasone), CEP[10],[11] (lomustine [CCNU], etoposide, chlorambucil, and prednisolone), and PEP-C[12] (cyclophosphamide, etoposide, procarbazine, and prednisolone) should be considered. Intensive salvage chemotherapies must be planned in young fit patients with no or controlled comorbidities and good organ functions after detailed counseling
  6. Intensive salvage chemotherapy and autologous peripheral blood stem cell transplant (PBSCT) should be deferred, if possible (detailed discussion in the transplant section below).


Non-Hodgkin's lymphoma

High-grade non-Hodgkin's lymphoma

  1. Patients diagnosed with high-grade non-Hodgkin's lymphomas (NHLs) such as diffuse large B cell lymphoma, anaplastic large cell lymphoma, and Burkitt's lymphoma should be treated with high-dose chemotherapy on their own merits
  2. Patients need to be evaluated for organ dysfunction to reduce toxicities and any comorbidity must be strictly controlled. Patients and their relatives should be counseled in detail about toxicities and possibilities of infective complications
  3. In patients with poor PS status or uncontrolled comorbidities, less intensive regimens such as cyclophosphamide, vincristine, and prednisolone or oral chemotherapy regimens such as DECC, CEP,[10],[11] oral metronomic chemotherapy (cyclophosphamide, etoposide, and prednisolone),[13] methotrexate, and lenalidomide[14] can be considered
  4. Relapsed refractory cases can be treated with oral chemotherapy or oral targeted agents, while salvage chemotherapy and auto-PBSCT should be considered only in a select group of patients.


Low-grade non-Hodgkin's lymphomas

  1. Patients with low-grade NHL are noted, especially in the older population. These usually require treatment in specific situations such as the presence of B symptoms, bulky disease, pancytopenia, and repeated infections[15]
  2. Rather than administering high-dose chemotherapy, oral chemotherapeutic agents such as chlorambucil, cyclophosphamide, and prednisolone can be given
  3. Even though intravenous chemotherapy regimens such as BR (rituximab and bendamustine) cause cytopenias less frequently,[16] they should still be given in patients with good ECOG PS only after detailed counseling
  4. Monoclonal antibodies such as rituximab (anti-CD20) are the standard of care in B-cell NHLs, which cause prolonged immunosuppression,[17] and should be administered only after discussing the pros and cons with patients.


Myeloma

  1. When treating these patients, it is important to distinguish patients as transplant eligible and transplant ineligible
  2. Instead of parenteral regimens, including proteasome inhibitors (bortezomib and carfilzomib)[18] which require patients to visit the daycare frequently, oral regimens such as IMiDs (thalidomide, lenalidomide, and pomalidomide) with steroid (prednisolone/dexamethasone) can be given
  3. If proteasome inhibitors are to be used, subcutaneous bortezomib can be used as home therapy, rather than the intravenous formulation[19]
  4. In patients in whom IMiDs are contraindicated, some of the oldest regimens such as melphalan–prednisolone[20] can be given
  5. Prolonged lenalidomide or melphalan are to be avoided in case of patients who are planned for auto-PBSCT
  6. Intensive treatments such as high-dose melphalan followed by auto-PBSCT should be deferred, and patients should be put on maintenance therapy (bortezomib or lenalidomide). In patients planned for autologous PBSCT, long-term lenalidomide can be a problem and may need to be tackled with plerixafor. Subcutaneous bortezomib at home can be given
  7. In relapsed refractory cases, oral therapy such as IMiDs, melphalan, steroids, and targeted agents (panobinostat)[21] should be considered rather than intensive salvage therapies.


When oral therapies are substituted for intravenous therapies, monitoring as suggested earlier with tele- or videoconferencing should be done and questionnaire can be prepared to assess toxicities and efficacy.

Leukemia

Acute myeloid leukemia

  1. Acute myeloid leukemia (AML) patients have a relatively high early mortality rate of 37.5% at 8 weeks[22] and also a high overall mortality rate of about 76% at 3 years.[23] In patients aged 65 years and older, these rates are higher than in the younger patients
  2. Except low-risk patients and a subset of low intermediate risk, majority of AML patients require allogeneic stem cell transplant in complete remission[24]
  3. Considering the high morbidity and mortality during induction, patients are to be selected carefully: young patients, good risk, no comorbidities or controlled comorbidities, and no underlying infections
  4. These intensive treatments should be performed only in institutional settings and after ensuring adequate support of blood products
  5. Those patients with intermediate high risk or high risk, complex or monosomal karyotype, secondary AML (underlying myelodysplastic syndome [MDS]), induction failure, etc., should be treated with less intense therapies such as hypomethylating agents (decitabine and azacytidine)[25] or targeted agents (e.g., for FLT3-ITD, midostaurin, KIT mutation, or BCR-ABL-dasatinib)[26]
  6. Decision for allogeneic stem cell transplant should be made only after detailed counseling of the patient and family members.


Acute lymphoblastic leukemia

  1. The median age of acute lymphoblastic leukemia (ALL) diagnosis is about 15 years, while above the age of 55 years, approximately 20% of patients are diagnosed. However, around 50% of deaths due to ALL are seen in the population above 55 years of age. The 5-year overall survival is approximately 20% in adults diagnosed with ALL[27]
  2. Newly diagnosed patients are to be treated cautiously during induction therapy
  3. Intensive chemotherapy such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone should be reserved for young adults
  4. Those with disease in remission can be considered for maintenance oral chemotherapy with methotrexate/6 mercaptopurine (6-MP)
  5. Philadelphia-positive ALL can be treated with oral tyrosine kinase inhibitor (TKI) (dasatinib)[28]
  6. Relapsed refractory cases to be managed with oral chemotherapy.


Chronic myeloid leukemia

  1. Chronic myeloid leukemia in the chronic phase and accelerated phase can be continued with oral TKIs (imatinib, dasatinib, and nilotinib)
  2. Follow-up visits can be scheduled less frequently and can be done via tele- or videoconferencing[4]
  3. Patients in blast crisis can be managed with second -generation TKI (dasatinib or nilotinib), or in case of T315I mutation ponatinib, as a bridge to transplant[29],[30],[31]
  4. Candidates for allogeneic transplant must be carefully evaluated.


Chronic lymphoid leukemia

  1. Many of chronic lymphoid leukemia patients are under surveillance unless there are indications to start treatment (B-Symptoms, bulky lymphadenopathy, progressive marrow failure, massive or symptomatic splenomegaly, autoimmune complications, etc.)[32]
  2. Regular follow-up can be done telephonically or by videoconferencing
  3. Those who require treatment can be started appropriately based on risk stratification after detailed discussion
  4. Chemotherapy regimens such as BR should be considered after detailed evaluation and counseling
  5. Oral agents such as chlorambucil[33] and ibrutinib[34] can be considered to treat patients on OPD basis.


Autologous and allogeneic transplants

Stem cell transplant is one of the most intensive treatments and infective complications are much higher. Another concern is requirement of blood products.

  1. For transplant, whether autologous or allogeneic, candidates should be selected considering ECOG PS, comorbidities, organ function, etc.
  2. When doing such intensive treatment, risk must be weighed against outcome
  3. These must be done in institutions with good blood bank when ensuring availability of voluntary donors and facility of irradiating blood products in house
  4. Patients must be properly isolated to avoid exposure to COVID-19 positive or suspected cases
  5. In allogeneic transplant, if the family donor is available, pretransplant isolation of both patient and donor should be done to avoid exposure to COVID-19 cases; as if the donor gets infected and the patient has already received conditioning regimen, it can result in major complications
  6. Matched unrelated donor transplants can be problematic in the present pandemic, where a distant donor might get infected with COVID-19 or might deny stem cell donation due to other logistic issues, especially if the donor is from another country. In this case, transportation of stem cells can be another issue. It is prudent to obtain stem cells at the transplant center prior to starting conditioning regimen and these must be appropriately cryopreserved to maintain viability.



  Conclusion Top


The current COVID-19 pandemic has affected health-care globally as well as in India. Besides the burden on health-care givers, it is causing multiple problems in delivering treatments in other specialties such as cardiology, oncology, and nephrology. As we are learning to treat cancer patients in the middle of this crisis, we must understand that we should make rational clinical decisions based on our experiences. Our aim is to reduce COVID-19 infection in our patients, but with the least compromise in patient outcome.[35]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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