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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 5  |  Page : 59-64

Treating hematolymphoid malignancies during COVID-19 in India: Challenges and potential approaches


1 Regional Advanced Centre for Transplant, Hemato-Lymphoid Oncology and Marrow Diseases, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
2 Department of Clinical Hematology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission03-Apr-2020
Date of Decision05-Apr-2020
Date of Acceptance08-Apr-2020
Date of Web Publication25-Apr-2020

Correspondence Address:
Chepsy C Philip
Regional Advanced Centre for Transplant, Hemato-Lymphoid Oncology and Marrow Diseases, Believers Church Medical College Hospital, Thiruvalla - 689 103, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_114_20

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  Abstract 


The rapidity of both the geographical expansion and the sudden increase in the numbers of COVID-19 cases poses critical challenges to public health and has the potential to severely limit non COVID-19 medical care. With early reports from China & Italy suggesting that patients with hematolymphoid malignancies along with the other cancers are at the highest risk of severe infection compared to the normal population; it is a challenge on how to best manage such patients in India. There is a lack of reliable evidence and it is yet unclear as to what the best practices are with regards to patients with hematolymphoid malignancies in this time of crisis. We present a collection of best practices and guidance from literature search, society resources and communications with experts. Despite the unique and unprecedented nature of this challenge, our approach should reflect the principles of beneficence and non-maleficence as outlined in the Hippocratic oath.

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


How to cite this article:
Philip CC, Devasia AJ. Treating hematolymphoid malignancies during COVID-19 in India: Challenges and potential approaches. Cancer Res Stat Treat 2020;3, Suppl S1:59-64

How to cite this URL:
Philip CC, Devasia AJ. Treating hematolymphoid malignancies during COVID-19 in India: Challenges and potential approaches. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Jun 3];3, Suppl S1:59-64. Available from: http://www.crstonline.com/text.asp?2020/3/5/59/283287




  Introduction Top


There is now both clarity and evidence regarding the threat to global health posed by the respiratory disease, now given the name Coronavirus Disease 2019 (COVID-19).[1] As of April 4, there are 207 countries, areas, or territories affected with 976,249 confirmed cases and 50,489 confirmed deaths.[2] These include the 2547 confirmed cases and 62 deaths from India.[3] COVID-19 which rapidly spread from a single city in China to the entire country within 30 days is now escalating across the globe and has been declared a pandemic by the World Health Organization.[4] The rapidity of both the geographical expansion and the sudden increase in the numbers of cases poses critical challenges for the public health, research, and medical communities.

India is now in the midst of a national lockdown as part of an effort to check the spread of this novel Coronavirus named SARS-CoV-2.[5] Lockdown and social distancing aim to flatten the curve of new infection, thereby limiting a surge of demand on the health-care services. There is a potential association with mortality and health-care service burden.[6] Careful utilization is needed given the emerging reports from developed countries regarding a shortage of health-care resources.[7]

The outbreak has the potential to severely limit non-COVID-19 medical care. Early reports from China and Italy suggest that patients with hematolymphoid malignancies along with other cancers are at the highest risk of severe infection compared to the normal population; it is a challenge on how to best manage such patients in India. There are no approved medicines or vaccines. The utility of tocilizumab has been reported, and the possible role of natural killer-cellular therapy is being pursued.[8],[9],[10] However, there is a lack of reliable evidence, and it is yet unclear, what are the best practices with regard to patients with hematolymphoid malignancies in this time of crisis.

We present a curated collection of expert guidance from the literature search, COVID resources from leading hematology and oncology societies as well as personal communications and conversations with expert colleagues within and outside the country.

This is not an official guidance and it remains the responsibility of each medical professional to decide on the appropriate advice, diagnosis, and line of care for patients.


  Materials and Methods Top


We searched PubMed using the Mesh headings (“Hematology” [Mesh] OR “Neoplasms” [Mesh]) AND “COVID-19” (Supplementary Concept). We supplemented these with a search on Google Scholar with “allintitle: Cancer OR hematology OR haematology “covid.””

A total of 41 articles were identified. One was in Chinese. Four articles were related to hematolymphoid malignancies. One interim guidance and one correspondence were specific to care in a hematolymphoid oncology setting. We also borrowed from personal correspondence with hematology experts and from resources available in leading hematology society webpages.


  Discussion Top


China and Wuhan experience

Based on the initial reports, along with older persons, given the immunosuppression because of the disease and the treatment, patients with hematolymphoid malignancies along with the other cancers were at the highest risk of severe infection.[11] These patients exhibited significantly more fever, cough, and dyspnea, higher C-reactive protein levels and procalcitonin, and lower hemoglobin, lymphocyte and platelet counts.[12],[13],[14] Coagulopathy was a key feature noted in poor outcomes with heparin being recommended, particularly in acute lymphoblastic leukemia (ALL).[14-16] The pulmonary lesions conform to imaging features in COVID but could progress rapidly. Patients also have a longer time to viral clearance and experience a longer incubation period suggestive of the need for better imaging modalities like computed tomography imaging earlier on.[17],[18] Besides visits to the hospital increasing the risk of infection, COVID-19 mortality rates in populations that had low access to health-care resources exceeded mortality rates in areas with better access.[6]

Faced with an acute burden on resources, patients with malignant hematological diseases were divided into two categories. For patients with stable or chronic disease, treatments were deferred, imposing a watch and wait strategy. For patients in urgent need of treatment, less immunosuppresive and more focused therapies like oral chemotherapy or targeted agents were substituted when possible, aimed at reducing the need for blood transfusions and inpatient admissions.[19] In the myelosuppressive phase posttherapy, if clinical improvement was not noted, then viral load was monitored in those affected with COVID.[18] Of note, tocilizumab was used successfully in a patient with myeloma; this needs to be studied further.[8]

Challenges

The outbreak has the potential to severely limit the number of beds available for non-SARS-CoV-2 medical care.[20] Patients with cancers, particularly those with hematolymphoid malignancies, could be at increased risk of severe COVID-19 disease.[14],[21] With lockdown and social isolation measures, delivery of cancer therapies could be disrupted. This is particularly relevant in India where people travel long distances to receive cancer care.[22] In smaller centers, particularly in low middle-income countries, it is also likely to affect diagnostic services since there is often dependence on an offsite laboratory. Emerging data show a disproportionately higher COVID infection rate among the health-care workforce.[23] This coupled with a reported shortage in medical capacity and protection kits that could trigger a fatal downward spiral as experienced in other countries.[24],[25] In the event of donor and health-care capacity restraint, there is also a threat to the supply of blood components further affecting the ability to deliver myelosuppressive therapies. Beyond these, the predicted negative economic effects and the reallocation of resources are anticipated to adversely affect an out-of-pocket health-care system like ours, wherein many patients are dependent on governmental and nongovernmental assistance further restricting treatment affordability.[26],[27]

These limit accessibility, availability, accuracy, and affordability of care for patients with hematolymphoid malignancies.

Approaches

General

  1. Patient awareness: Each patient has to be made aware of their vulnerability to COVID-19 infection. The need to adhere to universal precautions has to be emphasized (social distancing, frequent handwashing, use of sanitizers, and face mask)[28],[29]
  2. Resource allocation: A rotation policy keeping a fraction of health-care workers in reserve could be a strategy. This limits the exposure of personnel and also helps maintain an adequate replacement pool in the likelihood of frontline health-care workers getting infected. Certain countries are also deploying retired doctors and those in specialist training to share the responsibilities.[30] Efficient pathways for stakeholder coordination in a dynamic scenario also need to be adopted[31]
  3. Equipment: A public–private partnership to mass-produce protection and diagnostic kits as well as ventilators could be formulated as a national policy. There are valuable approaches and experiences to be adopted from other countries[32]
  4. Telemedicine and e-clinics: Strategies to leverage technology should be adjusted to local capabilities. Importantly, these limit travel and exposure while facilitating uninterrupted care of stable patients with chronic diseases.[33],[34] Patients should be updated and advised to utilize such channels. Interval phone calls or telemedicine consults also allow to monitor patient tolerance and outcomes[31]
  5. Laboratory evaluation: Clustering into waiting areas for phlebotomy again has the potential to facilitate the spread of the infection. Based on the clinical judgment of the treating physicians, it might be reasonable to defer phlebotomies. Alternately, remote laboratories in proximity to patient residence or hospital off-site phlebotomy facilities, for example, hospital car parks where patients can queue within their cars minimizing contact with others are also strategies[12]
  6. Ethical consideration: Resource allocation during disasters is a challenge and could be guided by a multidisciplinary ethical framework engaging with stakeholders in ethics, administration, and government among others[35],[36],[37]
  7. Treatment decisions: Therapies that can easily be paused and deferred should be agreed preferably with guidance through the national bodies or as a multidisciplinary institutional committee[12],[31]
  8. Supportive care:


  1. Growth factor support is recommended for patients to coincide with the period of their myelosuppression. The use of pegylated preparations would reduce hospital visits
  2. There are some reports of higher venous thromboembolism risk in COVID. Advice remains to continue prophylaxis and therapy as indicated. Recommendations support the use of heparin in place of oral and novel anticoagulants. Low molecular-weight heparin (LMWH) in place of unfractionated heparin (UFH) to shorten contact for prophylaxis, and UFH and LMWH for therapy in hospitalized critically ill patients because of the shorter half-life, are the suggested practices. The use of tranexamic acid is discouraged in disseminated intravascular coagulation.[38] No change in prophylactic practice for myeloma is yet suggested.


Specific

Therapeutic decisions need to be individualized, considering the disease, stage, age, and comorbidities.

Induction therapy

Indolent lymphomas and low-risk diseases: Watchful waiting should be the preferred strategy when possible. Treatment for asymptomatic patients with rituximab immunotherapy is not recommended, and when treatment is indicated, rituximab (R) immunotherapy rather than R-chemotherapy should be given consideration.[39]

High-grade lymphomas: R-CHOP continues to be the standard of care for diffuse, large B-cell lymphoma, and for older patients, R-mini-CHOP with growth factor support is recommended.[40]

Newly diagnosed acute myeloid leukemia (AML) and ALL: Treatment is considered emergent in most cases. Depending on institutional preparedness, experts suggest intensive induction chemotherapy in AML for eligible patients with 7 + 3 or similar. However, if a low-intensity therapy (such as hypomethylating agents ± venetoclax) is an option, there is a suggestion to prefer this treatment over 7 + 3 to minimize transfusions and utilization of inpatient beds.[41]

In ALL during induction, the use of steroids could be reduced but not stopped. Furthermore, if patients are at high risk for complications, dose-reducing daunorubicin (50%) or using a reduced dose peg-L-asparaginase could be considerations.[42] A tyrosine kinase inhibitor (TKI) with minimal steroid exposure is favored in the case of Philadelphia-positive+ ALL.

Chronic myeloid leukemia: Caution and care along with a continuation of TKI is recommended.[43]

Hodgkin disease: For advanced-stage disease, ABVD with an interim imaging to allow for the elimination of bleomycin in cycles 3–6 per the RATHL trial is the suggested practice. For early-stage, unfavorable disease, ABVD × 4–6 cycles could be a consideration because of the fewer number of visits.[44]

Multiple myeloma: Recommendations from the international myeloma society include starting triplet therapy with bortezomib, lenalidomide, and dexamethasone (VRD), which can be extended until 6 cycles, followed by lenalidomide maintenance in patients requiring treatment. Cyclophosphamide could be a useful substitute to lenalidomide to limit myelosuppression. For transplant-ineligible patients, lenalidomide–dexamethasone is an option. Dexamethasone should be reduced to 20 mg weekly.

Postinduction (consolidation/maintenance) therapy

Unless the patient is actively affected with COVID, there are no suggestions to discontinue consolidation or maintenance.

Indolent lymphomas and low-risk diseases: Some experts have discontinued maintenance rituximab, especially in older patients and in younger patients with low immunoglobulin levels.[39]

AML: Consolidation/postremission therapy with high-dose cytarabine should continue to be offered to patients in complete remission, with consideration being given to decreasing the number of cycles to 3 instead of 4 and/or lowering the dose of cytarabine to 1.5 g/m2 instead of 3 g/m2.[41]

ALL: Broadly, the goal is to maintain an absolute neutrophil count >1000/mm3. Bridging with oral 6-MP and methotrexate to minimize myelosuppression in consolidation could be an option. Some experts suggest a 50% dose reduction of glucocorticoids during maintenance.[42]

Myeloma: For transplant eligible patients, frontline autologous stem cell transplant should be postponed if possible. For high-risk patients on VRD maintenance, continuing therapy is recommended, but it can be changed to Rd (lenalidomide + dexamthasone) if appropriate.

Relapsed/resistant disease

There needs to be a clear discussion with the patient and family regarding the potential utility and support prior to such treatments. For patients without proliferative disease or significant transfusion dependence, therapy may be temporarily postponed, particularly, in a resource-limited setting like ours, decisions will need to be individualized.

Lymphoma: Lenalidomide-based regiments are being utilized by some experts in this setting.[40]

AML: Few experts still consider salvage intensive re-inductions, but the potential benefit must be weighed against the prolonged hospital stay, visitor restriction, as well as the potential blood product shortage.

ALL: Experts suggest utilizing inotuzumab or quickly transitioning blinatumomab or nelarabine/nelarabine-based regimens for management. Access to these medications is a limitation presently in India, but if can be arranged, these agents would be preferred to cytoreductive chemotherapies. Patients who achieve CR2 should be considered for allogeneic transplant expeditiously despite the pandemic.

Transplantation: Nonurgent transplants should be deferred. Those affected or suspected with symptoms or travel history should be deferred and supported by negative polymerase chain reaction results prior to taking up for transplant. All stem cell donors should be screened in detail for travel, and if symptomatic, they should be tested for COVID-19.[45]

Sibling donor transplantation for high-risk malignancies should be expedited as early as possible. In case of matched unrelated donor transplantation, COVID-19 is a serious concern to the collection, transport, and storage of stem cells and may be a serious challenge. Securing stem cell product access by freezing the product before the start of conditioning or to have an alternative donor as a backup are current suggestions.[46]

Limitations

We acknowledge that the source and strength of these suggestions are not based on high-quality evidence but are mostly viewpoints (documented/personal communications) drawn primarily from information available on society web pages and the limited experience from China and few other centers. However, these could help colleagues in their decision-making and form a framework while awaiting more specific recommendations from national societies.


  Conclusion Top


It is important that national guidelines and recommendations are adhered to. However unique our challenges, all our approaches need to remain consistent with the Hippocratic oath, which is first to do no harm and provide treatment to patients in need and for their good.[47] It is also the time now more than ever to unite and collaborate, sharing the knowledge gained and honoring our obligation to the global community.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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