Populations	Interventions	Comparators	Outcomes
Individuals: With allogeneic stem cell transplant	Interventions of interest are: Donor lymphocyte infusion	Comparators of interest are: Standard treatment	Relevant outcomes include: Overall survival Change in disease status
Individuals: With allogeneic stem cell transplant	Interventions of interest are: Modified (genetic or other ex vivo modification) donor lymphocyte infusion	Comparators of interest are: Standard treatment	Relevant outcomes include: Overall survival Change in disease status

Background

Approximately 40% to 60% of patients who receive a donor lymphocyte infusion (DLI) develop graft-versus-host disease (GVHD), and the development of GVHD predicts a response to the DLI. Treatment-related mortality after DLI is 5% to 20%. There does not seem to be a correlation between the type of hematologic malignancy for which the DLI was given and the development of GVHD.¹ The risk of development of GVHD is related, in part, to DLI dose and therapy before DLI.

DLI may be used for various indications such as relapse after allogeneic hematopoietic stem cell transplantation (HSCT), to prevent disease relapse in the setting of T cell‒depleted grafts or nonmyeloablative conditioning regimens, or to convert mixed to full donor chimerism. Management of relapse, which occurs in approximately 40% of all hematologic malignancy patients, is the most common indication for DLI.²

The literature is heterogeneous for reporting methods of cell collection, indication (eg, planned after chemotherapy, in early relapse), cell dose infused, and cell subtype used.¹ In addition, many studies include multiple diseases with little information on disease-specific outcomes; however, DLI is used in nearly all hematologic malignancies for which allogeneic HSCT is performed, including chronic myeloid leukemia, acute myeloid and lymphoblastic leukemias, myelodysplastic syndromes, multiple myeloma, and Hodgkin and non-Hodgkin lymphoma.

Regulatory Status

The U.S. Food and Drug Administration regulates certain human cells, tissues, and cellular and tissue-based products under the legal authority of section 361 of the Public Health Service Act (42 USC 264). This section authorizes the Surgeon General, with the approval of the Secretary of the U.S. Department of Health and Human Services, to make and enforce such regulations as judged necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the United States or from state to state. According to Addendum 7342.007—Imported Human Cells, Tissues, and Cellular and Tissue-based Products (HCT/Ps), umbilical cord blood stem cells, peripheral blood stem cells, lymphocytes (donor lymphocytes for infusion, T cells) are identified by product code 57M.P.

Related Policies

• None

3. Donor lymphocyte infusion is considered investigational as a treatment of non-hematologic malignancies following a prior allogeneic HSCT.

4. Genetic or other modification of donor lymphocytes is considered investigational.


Medicare Coverage:
Per National Coverage Determination (NCD) for Stem Cell Transplantation 110.23, CMS has determined that Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will be covered pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study for certain limited conditions. Medicare payment for these beneficiaries will be restricted to patients enrolled in a CMS approved clinical study. Bone marrow and peripheral blood stem cell transplantation is a process which includes mobilization, harvesting, and transplant of bone marrow or peripheral blood stem cells and the administration of high dose chemotherapy or radiotherapy prior to the actual transplant. The NCD does not address donor lymphocyte infusion post Allogeneic Hematopoietic Stem-Cell Transplant for Malignancies.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Donor lymphocyte infusion for Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.

For additional information on stem cell transplantation, refer to National Coverage Determination (NCD) for Stem Cell Transplantation 110.23. Available to be accessed at CMS National Coverage Determinations (NCDs) Alphabetical Index search page: https://www.cms.gov/medicare-coverage-database/indexes/ncd-alphabetical-index.aspx.

Medicaid Coverage:

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Settings considered high risk for relapse include T cell‒depleted grafts or nonmyeloablative (reduced intensity conditioning) allogeneic hematopoietic stem cell transplantation).


[RATIONALE: This policy was originally created in 2004 and has been updated regularly with searches of the PubMed database. The most recent literature review was performed for the period of July 23, 2020

Several review articles summarize studies that have reported the use of donor lymphocyte infusion (DLI) for the treatment of patients with hematologic malignancies that relapse following allogeneic hematopoietic stem cell transplantation (HSCT).^1-3

Several large series report outcomes of patients with relapsed CML after receiving DLI.^4-9 These studies comprise more than 1000 patients, approximately half of whom had only molecular or cytogenetic relapse at the time of DLI.¹ The cell doses varied among patients, with some receiving multiple DLI infusions and others, planned dose escalations. Despite these variations, a molecular or cytogenetic CR was achieved in 74% of patients (746/1007). Overall survival (OS) at 3 or more years ranged from 53% to 95%,² was 64% at 5 years, and was 59% at 10 years after DLI in another series.⁹

The role of DLI in CML has recently changed because the use of tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment by keeping the disease under control instead of proceeding to HSCT. However, for patients who develop resistance to TKIs or are unable to tolerate the adverse effects, HSCT and DLI may be an option to manage the disease.

Acute Leukemias, Myelodysplasia, and Other Myeloproliferative Diseases
In a 2013 systematic review, El-Jurdi et al evaluated 39 prospective and retrospective studies on DLI for relapse after HSCT for lymphoid malignancies including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), multiple myeloma, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL).¹⁰ No randomized controlled studies were identified. Studies identified were heterogeneous thus limiting interpretation of the review. Reported pooled proportions of CR (95% confidence interval [CI]) were 27% (16% to 40%) for ALL, 55% (15% to 92%) for CLL, 26% (19% to 33%) for multiple myeloma, 52% (33% to 71%) for NHL, and 37% (20% to 56%) for HL.

An observational study comparing different treatments for relapse reported on 147 consecutive patients who relapsed after allogeneic HSCT for myelodysplastic syndrome.¹¹ Sixty-two patients received HSCT or DLI, 39 received cytoreductive treatment, and 46 were managed with palliative or supportive care. Two-year rates of OS were 32%, 6%, and 2%, respectively (p<.001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% CI, 1.26 to 2.67; p=0.002), relapse within 6 months (HR=2.69; 95% CI, 0.82 to 3.98; p<0.001), progression to acute myelogenous leukemia (HR=2.59; 95% CI, 1.75 to 3.83; p<0.001), and platelet count less than 50 g/L at relapse (HR=1.68; 95% CI, 1.15 to 2.44; p=0.007). HSCT or DLI was found to be an independent factor that favorably impacts OS (HR=0.40; 95% CI, 0.26 to 0.63; p<0.001).

Acute Myelogenous Leukemia
DLI for patients with relapsed acute myelogenous leukemia (AML) after allogeneic HSCT has resulted in overall remission rates ranging from 15% to 42%, with an OS of 15% to 20%. (For comparison, a second HSCT in this group of patients results in 10% to 35% long-term survival with a treatment-related mortality of approximately 50%.) Patients with lower initial disease burden, reduction in the tumor burden with chemotherapy before DLI, and favorable cytogenetics appear to have more benefit with DLI.

A large retrospective analysis from the European Blood and Marrow Transplant Group compared OS in 399 patients with AML with posttransplant relapse who either were treated with DLI (n=171) or were not (n=228).¹² Patients who received DLI had an improved 2-year OS compared with those who did not, (21%±3% vs 9%±2%, respectively; p<0.001).

A 2015 large retrospective series from the Center for International Blood and Marrow Transplant Research (CIBMTR) reported outcomes of 1788 AML patients who relapsed after allogeneic HSCT in CR1 or CR2, among whom 1231 (69%) received subsequent intensive therapy that included DLI.¹³ Among the 1231 patients who received treatment, 660 (54%) received chemotherapy alone; 202 (16%) received DLI with or without chemotherapy; and 369 (30%) received a second allogeneic HSCT with or without additional chemotherapy or DLI. Among all patients who received DLI, 87 (33%) survived more than 1 year after relapse; median survival was 7 months (range, 1-177 months). Cell-based therapy (DLI or second HSCT) resulted in significantly better postrelapse OS than chemotherapy alone. These results are consistent with other reports of DLI in patients who relapse after allogeneic HSCT to treat AML.

The literature for myelodysplasia syndromes (MDS) and other myeloproliferative diseases treated with DLI either after relapse or for mixed chimerism consists of small sample sizes, inconsistent pre-DLI therapy, and varied DLI cell doses, making it difficult to draw definite conclusions on outcomes.² However, it appears some patients attain durable remissions with DLI after posttransplant relapse.²

Warlick et al reported CR after DLI in 49% (17/35) patients with relapsed nonchronic myelogenous leukemia, including AML and MDS, after allogeneic HSCT.¹⁴ OS at 1 year was 30% and 19% at 2 years. The authors reported that a lower dose regimen of DLI was more tolerable and reduced graft-versus-host disease (GVHD) occurrence to 25% compared with 66% with higher dose DLI.

An analysis from the German Cooperative Transplant Study Group reported outcomes among a cohort of patients (N=154) who relapsed after undergoing allogeneic HSCT to treat AML (n=124), MDS (n=28), or myeloproliferative syndrome (n=2).¹⁵ All patients received a median of 4 courses of azacitidine, and DLI was administered to 105 (68%). OS among all patients was 29%±4% at 2-year follow-up, which compares favorably with other reports. The overall incidence of acute GVHD based on the total cohort (N=154) was 23%, and 31% in those given DLI (n=105).

Acute Lymphoblastic Leukemia
The graft-versus-tumor effect is thought to be less robust in patients with ALL than in the myeloid leukemias. Small studies have reported response rates to DLI ranging from 0% to 20% and OS rates of less than 15%.¹ By comparison, a second allogeneic HSCT provides a 5-year OS of 15% to 20%, with a treatment-related mortality rate of approximately 50%.¹

The clinically evident graft-versus-leukemia effect of DLI requires weeks to months to become apparent, and, because ALL is a rapidly proliferating disease, DLI only is unable to control the disease without a significant reduction in leukemia burden before DLI. Management of patients with relapsed ALL leading to the best OS is with a combination of salvage chemotherapy and DLI. Although it is not clear whether DLI adds benefit to salvage chemotherapy, long-term survivors have been reported with relapsed ALL who received both chemotherapy and DLI.²

Lymphomas
Studies in which patients received DLI for lymphomas consist of small numbers of patients and various histologies (both HL and high- and low-grade NHL). In general, the highest response rates have been seen in the indolent lymphomas. For NHL, too few patients have been reported with any single histologic subtype of lymphoma to give adequate information of the benefit of DLI for a specific lymphoma subtype.²

The largest series reported for NHL (N=21) using DLI showed response rates in 3 of 9 patients with high-grade NHL, 1 of 2 patients with mantle cell lymphoma, and 6 of 10 patients with low-grade disease.¹⁶

A series of 14 patients with multiply relapsed HL who received reduced-intensity conditioning allogeneic HSCT and DLI showed a CR of 57% and 2-year survival of 35%.¹⁷

Multiple Myeloma
Observational data suggest a graft-versus-tumor effect in multiple myeloma, because the development of GVHD has correlated with response in several analyses.²

Allogeneic HSCT is currently considered experimental for this indication (see evidence review 8.01.17 on HSCT for plasma cell dyscrasias including multiple myeloma). Most patients with multiple myeloma who undergo HSCT receive an autologous HSCT. In addition, the overall role of HSCT for multiple myeloma is currently changing with the advent of highly active novel agents like lenalidomide and bortezomib.

Five studies reporting the role of DLI in relapsed multiple myeloma consist of patients ranging in number from 5 to 63,^18-22 with the highest response to DLI being reported as 62%, with approximately half of the responders attaining a CR.² One confounding factor for high response rates for multiple myeloma treated with DLI is that corticosteroids used for treating GVHD have a known antimyeloma effect, which could potentially enhance response rates in these patients.¹

Section Summary: Donor Lymphocyte Infusion
There are a few nonrandomized comparative studies and numerous case series of DLI treatment for various hematologic malignancies and other myeloproliferative disorders. The nonrandomized studies, in patients with acute leukemia and myelodysplastic syndrome, report higher response rates for patients treated with DLI than with alternatives. The case series report higher response rates than expected for relapsed disease from historical controls. Although there are no high-quality RCTs for DLI treatment, this evidence allows the conclusion that response rates improve with DLI treatment for patients with previous HSCT treatment and relapsed disease.

In a phase 2 study, donor lymphocytes were treated with rapamycin ex vivo to produce rapamycin-resistant DLIs.²⁴ Forty patients undergoing low-intensity HSCT for hematologic malignancy were treated preemptively with chemotherapy and DLI. There were no infusional toxicities or serious events attributable to DLI. Classical acute CVHD occurred in 4 of 40 patients. By the end of the study (follow-up range, 42-84 months), 18 of 40 patients remained in sustained remission.

A phase 1 study evaluated patient response to infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene.²⁵ Three patients were enrolled in the trial and received a single DLI. No local or systemic toxicity related to the gene-transfer procedure was observed. Two patients achieved stable disease. No patient had severe GVHD requiring systemic steroid and/or ganciclovir administration. Tyrosine kinase cells were detected in the peripheral blood of all 3 patients by polymerase chain reaction, but did not persist more than 28 days.

Section Summary: Modified DLI
These early phase studies are insufficient to determine the efficacy of modified DLI in the treatment of hematologic malignancies. Randomized studies comparing modified DLI to standard treatment would be necessary to determine efficacy.

The evidence for modified (genetic or other ex vivo modification) donor lymphocytes in individuals who have been treated with an allogeneic HSCT includes case series. Relevant outcomes are overall survival and change in disease status. The case series demonstrate the feasibility of the technique and no serious adverse effects. Without a comparison to standard treatment, the efficacy of administering modified donor lymphocytes is unknown. The evidence is insufficient to determine the effects of the technology on health outcomes.

Supplemental Information

In response to requests, input was received from 1 academic medical center and 5 Blue Distinction Centers for Transplant while this policy was under review in 2011. There was general agreement with the policy statements, although 2 reviewers disagreed with the statement on the use of DLI in nonhematopoietic malignancies; one thought it was investigational and medically necessary and the other did not think this was investigational or medically necessary. One reviewer suggested adding Epstein-Barr virus‒associated posttransplant lymphoproliferative disease as a medically necessary indication for DLI. One reviewer commented on an evolving technique for use of ex vivo expansion of donor lymphocytes.

NCCN guidelines do not address the use of DLI in the treatment of acute myelogenous leukemia (v.1.2015).

NCCN recommendations for treating acute lymphoblastic leukemia (v.2.2014) state that DLI can be considered an option for patients in relapse after allogeneic HSCT (category 2A).²⁷

NCCN guidelines do not include the use of DLI in the treatment of non-Hodgkin lymphoma or Hodgkin lymphoma (v.2.2015).

NCCN recommendations for treating multiple myeloma (v.4.2015) state that DLI can be considered an option for patients who do not respond or are in relapse after allogeneic HSCT (category 2A).²⁸

U.S. Preventive Services Task Force Recommendations

Not applicable.]

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Donor Lymphocyte Infusion for Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant
Donor Leukocyte Infusion
Donor Lymphocyte Infusion
Buffy Coat Transfusion
Leukocyte, Donor Infusion
Lymphocyte Infusion, Donor
Infusion, Donor Leukocyte
Transfusion, Donor Leukocyte

References:
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2. Tomblyn M, Lazarus HM. Donor lymphocyte infusions: the long and winding road: how should it be traveled? Bone Marrow Transplant. Nov 2008;42(9):569-579. PMID 18711351

3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Technology Assessment 1997; Tab 22.

4. van den Brink MR, Porter DL, Giralt S, et al. Relapse after allogeneic hematopoietic cell therapy. Biol Blood Marrow Transplant. Jan 2010;16(1 Suppl):S138-145. PMID 19857588

5. Simula MP, Marktel S, Fozza C, et al. Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy. Leukemia. May 2007;21(5):943-948. PMID 17361226

6. Dazzi F, Szydlo RM, Cross NC, et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. Oct 15 2000;96(8):2712-2716. PMID 11023502

7. Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood. Jul 15 2002;100(2):397-405. PMID 12091328

8. Fozza C, Szydlo RM, Abdel-Rehim MM, et al. Factors for graft-versus-host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose. Br J Haematol. Mar 2007;136(6):833-836. PMID 17341269

9. Radujkovic A, Guglielmi C, Bergantini S, et al. Donor lymphocyte infusions for chronic myeloid leukemia relapsing after allogeneic stem cell transplantation: may we predict graft-versus-leukemia without graft-versus-host disease? Biol Blood Marrow Transplant. Mar 19 2015. PMID 25797175

10. El-Jurdi N, Reljic T, Kumar A, et al. Efficacy of adoptive immunotherapy with donor lymphocyte infusion in relapsed lymphoid malignancies. Immunotherapy. May 2013;5(5):457-466. PMID 23638742

11. Guieze R, Damaj G, Pereira B, et al. Management of myelodysplastic syndrome relapsing after allogeneic hematopoietic stem cell transplantation: a study by the French Society of Bone Marrow Transplantation and Cell Therapies. Biol Blood Marrow Transplant. Aug 6 2015. PMID 26256942

12. Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. Nov 1 2007;25(31):4938-4945. PMID 17909197

13. Bejanyan N, Weisdorf DJ, Logan BR, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant. Mar 2015;21(3):454-459. PMID 25460355

14. Warlick ED, DeFor T, Blazar BR, et al. Successful remission rates and survival after lymphodepleting chemotherapy and donor lymphocyte infusion for relapsed hematologic malignancies postallogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. Mar 2012;18(3):480-486. PMID 22155141

15. Schroeder T, Rachlis E, Bug G, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions-a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. Apr 2015;21(4):653-660. PMID 25540937

16. Morris E, Thomson K, Craddock C, et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. Dec 15 2004;104(13):3865-3871. PMID 15304395

17. Peggs KS, Sureda A, Qian W, et al. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes. Br J Haematol. Oct 2007;139(1):70-80. PMID 17854309

18. Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood. Nov 15 1997;90(10):4206-4211. PMID 9354693

19. Salama M, Nevill T, Marcellus D, et al. Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant. Dec 2000;26(11):1179-1184. PMID 11149728

20. Collins RH, Jr., Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. Feb 1997;15(2):433-444. PMID 9053463

21. Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood. Oct 1 1996;88(7):2787-2793. PMID 8839877

22. Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol. Aug 2000;18(16):3031-3037. PMID 10944138

23. Ciceri F, Bonini C, Marktel S, et al. Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood. Jun 1 2007;109(11):4698-4707. PMID 17327416

24. Fowler DH, Mossoba ME, Steinberg SM, et al. Phase 2 clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after low-intensity allogeneic hematopoietic cell transplantation. Blood. Apr 11 2013;121(15):2864-2874. PMID 23426943

25. Hashimoto H, Kitano S, Ueda R, et al. Infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene for recurrent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Int J Hematol. Jul 2015;102(1):101-110. PMID 25948083

26. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia. v.1.2015. 2015; http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed March, 2015.

27. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Acute Lymphoblastic Leukemia (v.2.2014). 2014; http://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed March, 2015.

28. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Multiple Myeloma (v.4.2015). 2015; http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed March, 2015.

29. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Acute Lymphoblastic Leukemia (v.5.2017). 2017; https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed October, 2017.

30. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia. v.2.2018. 2018; https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed October, 2017.

31. Negrin RS. Hematopoietic cell transplantation in chronic myeloid leukemia. In: UpToDate, Chao NJ, Rosmarin AG (Eds), UpToDate, Waltham, MA. (Accessed on October 6, 2017.)

32. Negrin RS. Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation. In: UpToDate, Chao NJ, Rosmarin AG (Eds), UpToDate, Waltham, MA. (Accessed on August 28, 2018.)

33. Negrin RS. Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation. In: UpToDate, Chao NJ, Rosmarin AG (Eds), UpToDate, Waltham, MA. (Accessed on August 28, 2019.)

34. Merker M, Salzmann-Manrique E, Katzki V, Huenecke S, Bremm M, Bakhtiar S, Willasch A, Jarisch A, Soerensen J, Schulz A, Meisel R, Bug G, Bonig H, Klingebiel T, Bader P, Rettinger E. Clearance of Hematologic Malignancies by Allogeneic Cytokine-Induced Killer Cell or Donor Lymphocyte Infusions. Biol Blood Marrow Transplant. 2019 Jul;25(7):1281-1292. doi: 10.1016/j.bbmt.2019.03.004. Epub 2019 Mar 13. .

35. Schuler E, Boughoufala S, Rautenberg C, Nachtkamp K, Dienst A, Fenk R, Haas R, Kondakci M, Germing U, Schroeder T, Kobbe G. Relapse patterns and treatment strategies in patients receiving allogeneic hematopoietic stem cell transplantation for myeloid malignancies. Ann Hematol. 2019 May;98(5):1225-1235. doi: 10.1007/s00277-019-03670-6. Epub 2019 Mar 29.

36. Negrin RS. Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation. In: UpToDate, Chao NJ, Rosmarin AG (Eds), UpToDate, Waltham, MA. (Accessed on July 27, 2020.)

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

38242