Transplant Consultation Timing Guidelines

Identify appropriate HCT referral timing based on disease characteristics

If allogeneic or autologous hematopoietic cell transplant (HCT) may be indicated for your patient, early referral for HCT consultation is a critical factor for optimal transplant outcomes. For many patients, there may be a narrow window of opportunity to proceed to transplant. Delays might preclude transplant or impair transplant outcomes.

The HCT consultation timing guidelines identify appropriate referral timing for allogeneic or autologous HCT based on a patient’s disease characteristics. In collaboration with you, the transplant center will evaluate the patient and coordinate HCT timing for eligible patients.

Hematopoietic stem cell transplant consideration includes both patient and disease characteristics. The HCT consultation includes risk-to-benefit consideration based on risk score assessments.

Age alone is not a contraindication due to advances in HCT. Older adults with selected comorbidities and good functional status can safely undergo HCT for curative intent with a relatively low and acceptable risk of non-relapse mortality.

If allogeneic transplant is potentially indicated, you should perform HLA typing of the patient and potential family donors at diagnosis. In addition, a preliminary unrelated donor search of the NMDP Registry® should be completed.

NMDP offers HLA Today at no cost to you or your patient to remove barriers to patient and family member HLA typing and a preliminary unrelated donor search.

NMDP and the American Society for Transplantation and Cellular Therapy (ASTCT) jointly developed the HCT consultation timing guidelines. The guidelines are based on current clinical practice, medical literature, National Comprehensive Cancer Network® (NCCN®) Guidelines for the treatment of cancer, and evidence-based reviews.[1,2]

Browse the disease-specific guidelines below or in these additional formats:

• Download Transplant Consultation Guidelines PDF
• Download the HCT Guidelines mobile app
• Access online mobile app
• Download Post-Transplant Guidelines PDF

Recommended Timing for Transplant Consultation

Adult Leukemias and Myelodysplasia

Acute Myeloid Leukemia (AML)

HCT consultation should take place early after initial diagnosis for patients with AML, including:

• Primary induction failure
• Measurable (also known as minimal) residual disease after initial therapy
• CR1 – except favorable risk AML [defined as: t(8;21)(q22;q22.1); RUNX1-RUNX1T1, inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, mutated NPM1 without FLT3-ITD, biallelic mutated]. Transplant consultation may be reasonable for favorable-risk AML patients with unusual or adverse co-mutations or cytogenetic alterations. Early referral for allogeneic HCT should also be considered for any patients in CR1 who are 60 years old or older; regardless of cytogenetic or genomic information.
• Antecedent hematological disease (e.g., myelodysplastic syndrome [MDS]), either based on prior clinical diagnosis or suggested by the presence of secondary-type somatic mutations on molecular testing
• Treatment-related leukemia
• First relapse
• CR2 and beyond, if not previously evaluated

AML transplant advances and outcomes data

Acute Lymphoblastic Leukemia (ALL) (adult defined as ≥40 years)

HCT consultation should take place early after initial diagnosis for patients with ALL including:

• Primary induction failure
• Measurable (also known as minimal) residual disease after initial therapy
• CR1
• First relapse
• CR2 and beyond, if not previously evaluated

ALL transplant advances and outcomes data

Myelodysplastic Syndromes (MDS)

• Any intermediate or high IPSS or IPSS-R score or moderate, high, or very high IPSS-M score
• Any MDS with poor prognostic features, including:
  • Treatment-related MDS
  • Refractory cytopenias
  • Adverse cytogenetics and molecular features
  • Transfusion dependence
  • Failure of hypomethylating agents or chemotherapy
  • Moderate to severe marrow fibrosis

MDS transplant advances and outcomes data

Chronic Myeloid Leukemia (CML)

• Inadequate hematologic or cytogenetic/molecular response to tyrosine kinase inhibitor (TKI) therapies
• Disease progression
• Intolerance to TKI therapies
• Accelerated phase
• Blast crisis (myeloid or lymphoid)
• T315I mutation

CML transplant advances and outcomes data

Myeloproliferative Neoplasms (MPN)

including primary myelofibrosis (PMF) and essential thrombocythemia or polycythemia vera that has progressed to MF (secondary MF)
High-resolution HLA typing and referral to HCT consultation is recommended at diagnosis for all patients with:

• DIPSS or DIPSS Plus Intermediate-1 (INT-1) or higher
• MIPSS70/MIPSS 70 plus version 2.0 intermediate-risk or higher
• Cytopenic subtype
• Young age
• High-risk features including high-risk mutations ( ASXL1, TP53), triple negative (lack of a driver mutation such as JAK2, MPL or CALR)
• Patients failing JAK inhibitor therapy

HCT is recommended upfront for patients with:

• DIPSS or DIPSS Plus Intermediate-2 (INT-2) and high-risk disease
• MIPSS70/MIPSS 70 plus version 2.0 high-risk disease
• Patients with DIPSS INT-1 or MIPSS70/MIPSS 70 plus version 2.0 intermediate-risk, cytopenic subtype, young age, high-risk features, including high-risk mutations (ASXL1, TP53), triple negative (lack of a driver mutation such as JAK2, MPL, or CALR) and those failing JAK inhibitor therapy should be considered for upfront HCT balancing patient preferences and clinical trial options

Chronic Lymphocytic Leukemia (CLL)

• Resistance or intolerance to BTK inhibitors and BCL2 inhibitors
• Richter's transformation

CLL transplant advances and outcomes data

Pediatric Leukemias and Myelodysplasia

Acute Myeloid Leukemia (AML)

HCT consultation should take place early after initial diagnosis for patients with AML including:

• Age <2 years at diagnosis
• Primary induction failure
• Measurable (also known as minimal) residual disease after initial therapy
• CR1 – except favorable risk AML [defined as: t(8;21)(q22;q22.1); RUNX1-RUNX1T1, inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, mutated NPM1 without FLT3-ITD or with FLT3-ITD^low, biallelic mutated CEBPA]
• Monosomy 5 or 7
• Treatment-related leukemia
• First relapse
• CR2 and beyond, if not previously evaluated

Pediatric AML transplant advances and outcomes data

Acute Lymphoblastic Leukemia (ALL) - <39 Years

High-resolution HLA typing is recommended at diagnosis for all patients

• Infant at diagnosis
  • unfavorable genetics
  • age <3 months with any WBC, or <6 months with WBC>300,000 at presentation or any infant with measurable (also known as minimal) residual disease (MRD)+ after consolidation
• Primary induction failure (M3 marrow) after achieving MRD negative status
• Presence of MRD after initial therapy; MRD ≥0.01% following consolidation (9–12 weeks from diagnosis)
• High/very high-risk CR1, including:
  • Philadelphia chromosome positive slow-TKI responders or with IKZF1 deletions; Philadelphia-like if MRD+ at end of consolidation, or persistently detectable low level of molecular disease
  • iAMP21 if MRD+ at end of consolidation
  • 11q23 rearrangement if MRD+ at end of consolidation
• First relapse with aim to transplant in CR2
• CR2 and beyond, if not previously evaluated, including:
  • all young adults in CR2
  • early relapse (≤36 months from diagnosis for medullary disease, ≤18 months from diagnosis for EMD)
  • MRD+ (>0.1% for medullary disease or equivalent for EMD) after re-induction (4–8 weeks from relapse)
  • T cell ALL
  • CR3 and beyond
• Chimeric antigen receptor therapy (CAR-T), including:
  • patients who receive CD19 4-1BB and achieve MRD negative CR if they have not already received HCT
  • patients who receive CD22 or other investigational therapies

Pediatric ALL transplant advances and outcomes data

Myelodysplastic Syndromes (MDS)

• At diagnosis for all subtypes

MDS transplant advances and outcomes data

Juvenile Myelomonocytic Leukemia (JMML)

• At diagnosis

Lymphomas

Non-Hodgkin Lymphoma

Follicular (FL)

• Transformation to diffuse large B-cell lymphoma
• Poor response to initial treatment
• Initial remission duration <24 months
• At relapse (CAR or alloHCT can be offered to patients with multiple relapsed FL)

Diffuse Large B-Cell

• Primary CNS lymphoma at diagnosis PIF or first relapse
• Primary induction failure, including residual PET avid disease
• First relapse
• CR2 or subsequent remission
• Double or triple hit (MYC and BCL-2 and/or BCL-6) – at diagnosis

High Grade B-Cell

• MYC and BCL-2 and/or BCL-6 rearrangements
• Primary induction failure
• CR1
• First relapse
• CR2 or subsequent remission

Mantle Cell

• At diagnosis
• At relapse
• Bruton’s tyrosine kinase (BTK) intolerant or resistant disease

Mature T-cell and NK Cell Lymphoma

• At diagnosis or CR1
• At relapse

Other High-Risk Lymphomas

• At diagnosis

Non-Hodgkin lymphoma transplant advances and outcomes data

Hodgkin Lymphoma

• Primary refractory disease
• First or subsequent relapse
• Brentuximab vedotin and check point inhibitor refractory and/or intolerant disease (for alloHCT)

Hodgkin lymphoma transplant advances and outcomes data

Other Malignant Diseases

Germ Cell Tumors

High-dose therapy with autologous stem cell support may be considered for patients with:

• Non-germinomatous germ cell tumors (NGGCTs) for refractory disease post induction chemotherapy as long as the patient has chemo-responsive disease and does not have bulky residual tumor
• Germinoma or NGGCT, if the patient has chemo-responsive disease to reinduction chemotherapy and does not have bulky residual tumor

Neuroblastoma

• INRGSS L2 at diagnosis
  • MYCN amplification
  • age >18 months with unfavorable histology and segmental chromosome aberration
• INRGSS stage M at diagnosis:
  • MYCN amplification
  • age >18 months at diagnosis
  • age 12–18 months with unfavorable histology, segmental chromosome aberrations, or diploid DNA content 

Ewing Family of Tumors

• Metastatic disease at diagnosis
• First relapse or CR2

Medulloblastoma

High-dose therapy with autologous stem cell support may be considered standard therapy for several infant (younger than 3 years of age) embryonal tumors as first line, including:

• Medulloblastoma
• Atypical teratoid rhabdoid tumor (AT/RT)
• Embryonal tumor with multilayered rosettes (ETMR)
• Primitive neuroectodermal/embryonal tumors, not otherwise specified (NOS)

High-dose therapy with autologous stem cell support may be considered at relapse for patients with:

• Embryonal tumors as long as the patient has chemoresponsive disease to re-induction chemotherapy and does not have bulky residual disease

Plasma Cell Disorders

Multiple Myeloma

• At diagnosis
• At progression and/or relapse

Multiple myeloma transplant advances and outcomes data

Light Chain Amyloidosis

• At diagnosis
• At progression and/or relapse

POEMS Syndrome (Osteosclerotic Myeloma)

• At diagnosis

Non-Malignant Disorders

Immune Deficiency Diseases

(including severe combined immunodeficiency syndromes, Wiskott-Aldrich syndrome, Omenn syndrome, X-linked lymphoproliferative syndrome, severe congenital neutropenia and others)

• At diagnosis or if detected on newborn screening

Immune deficiency diseases transplant outcomes data

Inherited Metabolic Disorders

(including Hurler syndrome, adrenoleukodystrophy and others)

• At diagnosis
• Adrenoleukodystrophy (ALD): following the diagnosis of the cerebral form of ALD

Inherited metabolic disorders transplant outcomes data

Hemoglobinopathies

Sickle Cell Disease (SCD)

• Children (especially under age 13) with available matched sibling donors
• All patients with aggressive course (stroke, end-organ complications, frequent pain crises)
• All patients with an alternative donor option and any of the following:
  • Stroke or silent cerebral infarct or cognitive impairment >24 hours
  • Abnormal transcranial Doppler (TCD) velocity of ≥ 200 cm/sec or > 185 cm/sec with intracranial vasculopathy
  • Frequent episodes of acute chest syndrome or severe vaso-occulusive pain crises or combination of both in the preceding 2–3 years
  • Regular red blood cell transfusions to prevent sickle cell disease complications
  • Tricuspid value regurgitant jet (TRJ) velocity ≥2.7 m/sec (mainly in adults)
  • Chronic pain ≥6 months (leg ulcers, avascular necrosis)

Sickle cell disease transplant advances and outcomes data

Transfusion-Dependent Thalassemias

• At diagnosis

Thalassemia transplant advances and outcomes data

Hemophagocytic Lymphohistiocytosis (HLH)

• At diagnosis

Severe Aplastic Anemia

• At diagnosis

Other Marrow Failure Diseases

(including Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Fanconi anemia, Dyskeratosis Congenita and others)

• Diamond-Blackfan Anemia: continued transfusion dependent anemia following a course of steroid therapy, development of significant infections, MDS/AML
• Shwachman-Diamond syndrome, Fanconi anemia, Dyskeratosis Congentia and others: development of cytopenias, transfusion dependence, or significant infections; high-risk cytopenic clones, high-risk somatic mutation patterns; MDS/AML

Severe aplastic anemia and other marrow failure syndromes transplant advances and outcomes data

Systemic Sclerosis

• At diagnosis or with diffuse disease, with increasing skin tightness score (modified Rodnan skin score, [mRSS]) and evidence of decrease ( <80%) in % predicted pulmonary function tests: forced vital capacity (FVC) and/or diffusion capacity (DLCO)

Multiple Sclerosis (MS)

• After MS relapse, with ≥2 relapse episodes in past 3 years, while on disease modifying therapy. Refer patient prior to progression of severe disability: patient must be able to walk 100 meters (with unilateral assistance: cane, crutch or brace).

Disease-Specific Experts

NMDP would like to acknowledge the following disease-specific experts who review and update these guidelines.

• AML: Christopher Gibson, MD, Dana-Farber Cancer Institute; Katherine Tarlock, MD, Seattle Children’s Hospital
• ALL: Zachariah DeFilipp, MD, Massachusetts General Hospital; Marie Bleakley, MD, PhD, Fred Hutchinson Cancer Center
• MDS: Zachariah DeFilipp, MD, Massachusetts General Hospital; Ann Dahlberg, MD, Fred Hutchinson Cancer Center
• CML: Vivian Oehler, MD, Fred Hutchinson Cancer Center
• MPN and MF: Rachel Salit, MD, Fred Hutchinson Cancer Center
• CLL: Mazyar Shadman, MD, MPH, Fred Hutchinson Cancer Center
• JMML: Mignon Loh, MD, Seattle Children’s Hospital
• Plasma cell disorders: Anita D’Souza, MD, Medical College of Wisconsin
• NHL: Bhagirathbhai Dholaria, MD, Vanderbilt-Ingram Cancer Center
• HL: Medhi Hamadani, MD, Medical College of Wisconsin
• Neuroblastoma: Julie Park, MD, St. Jude Children’s Research Hospital
• Ewing Family: Douglas Hawkins, MD, Seattle Children’s Hospital
• Medulloblastoma and Germ Cell Tumors: Girish Dhall, MD, University of Alabama at Birmingham; Mohamed Abdelbaki, MD, Washington University St. Louis
• IDD: Chris Dvorak, MD, University of California San Francisco
• IMD: Paul Orchard, MD, University of Minnesota
• SCD: Elizabeth Stenger, MD, Emory University
• Thalassemia: Mark Walters, MD, University of California San Francisco
• HLH: Rebecca Marsh, MD, Cincinnati Children’s Hospital Medical Center
• SAA and other BMFs: Lauri Burroughs, MD, Fred Hutchinson Cancer Center
• Systemic Sclerosis: Keith Sullivan, MD, Duke Cancer Institute
• Multiple Sclerosis: George Georges, MD, Northwestern Medicine

References

1. Lee SJ, Klein J, Haagenson M, et al. (2007). High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood, 110(13), 4576-4583. DOI: 10.1182/blood-2007-06-097386.
2. Pidala J, Lee SJ, Ahn KW, et al. (2014). Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood, 124(16), 2596-2606. DOI: 10.1182/blood-2014-05-576041.
3. National Comprehensive Cancer Network. NCCN Guidelines. 2023. Access
4. Lindsley RC, Mar BG, Mazzola E, et al. (2015). Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood, 125(9), 1367–1376. DOI: 10.1182/blood-2014-11-610543.
5. Döhner H, Wei AH, Appelbaum FR, et al. (2022). Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood, 140(12), 1345–1377. DOI: 10.1182/blood.2022016867.
6. Guglielmelli P, Lasho TL, Rotunno G, et al. (2018). MIPSS70: Mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. Journal of Clinical Oncology, 36(4), 310–318. DOI: 10.1200/jco.2017.76.4886.
7. Kröger N, Bacigalupo A, Barbui T, et al. (2023). Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: Updated recommendations by the EBMT/ELN International Working Group. The Lancet Haematology, 11(1), E62–E74. DOI: 10.1016/s2352-3026(23)00305-8.
8. Herrera AF, Ahn KW, Litovich C, et al. (2021). Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma–type Richter syndrome. Blood Advances, 5(18), 3528–3539. DOI: 10.1182/bloodadvances.2021004865.
9. Jacobson CA, Chavez JC, Sehgal AR, et al. (2021). Axicabtagene Ciloleucel in relapsed or refractory indolent non-hodgkin lymphoma (Zuma-5): A single-arm, multicentre, phase 2 trial. The Lancet Oncology, 23(1), 91–103. DOI: 10.1016/s1470-2045(21)00591-x.
10. Fowler NH, Dickinson M, Dreyling M, et al. (2021). Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: The phase 2 Elara trial. Nature Medicine, 28(2), 325–332. DOI: 10.1038/s41591-021-01622-0.
11. Hamadani M, Ngoya M, Sureda A, et al. (2022). Outcome of allogeneic transplantation for mature T-cell lymphomas: Impact of donor source and disease characteristics. Blood Advances, 6(3), 920–930. DOI: 10.1182/bloodadvances.2021005899.
12. García-Sancho AM, Bellei M, López-Parra M, et al. (2022). Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: A multicenter GELTAMO/FIL study. Haematologica, 107(11), 2675–2684. DOI: 10.3324/haematol.2021.279426.
13. Pinto N, Naranjo A, Ding X, et al. (2023). Impact of genomic and clinical factors on outcome of children ≥18 months of age with stage 3 neuroblastoma with unfavorable histology and without mycn amplification: A children’s oncology group (COG) report. Clinical Cancer Research, 29(8), 1546–1556. DOI: 10.1158/1078-0432.ccr-22-3032.