Referral Timing Guidelines


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 2022 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 Be The Match Registry® should be completed.

The NMDP/Be The Match 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.

The National Marrow Donor Program® (NMDP)/Be The Match® 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:

Recommended Timing for Transplant Consultation


Adult Leukemias and Myelodysplasia


Acute Myeloid Leukemia (AML)

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

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
    • Early referral for allogeneic HCT should be considered any patient with AML in CR1 who is 60 years or older, regardless of cytogenetic or genomic information
  • Antecedent hematological disease (e.g., myelodysplastic syndrome (MDS))
  • 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)

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

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)

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

Any intermediate or high IPSS or IPSS-R 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 BCR-ABL-negative myeloproliferative neoplasms and later stages of polycythemia vera and essential thrombocytosis)
High resolution HLA typing is recommended at diagnosis for all patients 

Intermediate- or high-risk disease including:

  • High-risk cytogenetics
  • Poor initial response or at progression

Myelofibrosis (MF)

  • DIPSS Intermediate-2 (INT-2) and high risk disease
  • DIPSS Intermediate-1 (INT-1) with low platelet counts, refractory, red blood cell transfusion dependent, circulating blast cells >2%, complex cytogenetics
  • High risk driver mutations (ASXL1, EZH2, TET2, IDH1, IDH2, SRSF2, and TP53) or triple negative (lack of a driver mutation such as JAK2, MPL, or CALR) should be considered in decision making

Chronic Lymphocytic Leukemia (CLL)

  • Second or greater relapse following chemoimmunotherapy
  • Richter's transformation

CLL transplant advances and outcomes data

Pediatric Acute Leukemias and Myelodysplasia


Acute Myeloid Leukemia (AML) - Pediatric

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

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

  • Age <2 years at diagnosis
  • Primary induction failure
  • Measurable (also called minimal) residual disease after initial therapy
  • CR1 – except favorable risk AML [defined as: t(8;21)(q22;q21.1); RUNX1-RUNX1T1, inv(16)(p13. 1q22) or t(16;16)(p13. 1; q22); CBFB-MYH11, mutated NPM1 without FLT3-ITD or with FLT3-ITDlow, 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) - Age <15 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
  • Primary induction failure
  • Presence of measurable (also called minimal) residual disease after initial therapy
  • High/very high-risk CR1 including:
    • Philadelphia chromosome positive slow-TKI responders or with IKZF1 deletions; 
    • Philadelphia-like
    • iAMP21
    • 11q23 rearrangement
  • First relapse
  • CR2 and beyond, if not previously evaluated
  • Chimeric antigen receptor therapy (CAR-T)

Acute Lymphoblastic Leukemia (ALL) - Age 15-39 Years

High-resolution HLA typing is recommended at diagnosis for all patients
  • Primary induction failure
  • Presence of measurable (also called minimal) residual disease after initial therapy
  • High/very high-risk CR1 including:
    • Philadelphia chromosome positive or Philadelphia-like
    • iAMP21
    • 11q23 rearrangement
    • B-cell with poor-risk cytogenetics
  • First relapse
  • CR2 and beyond, if not previously evaluated

Pediatric ALL transplant advances and outcomes data

Myelodysplastic Syndromes (MDS) - Pediatric

  • At diagnosis for all subtypes

MDS transplant advances and outcomes data

Juvenile Myelomonocytic Leukemia (JMML)

  • At diagnosis

Resource for Patients:

Basics of Blood and Marrow Transplant (videos)

This series of short, easy-to-understand videos helps patients, caregivers and families learn what to expect before, during and after transplant. Available in English and Spanish.

Non-Hodgkin and Hodgkin Lymphomas


Follicular Lymphoma

  • Poor response to initial treatment
  • Initial remission duration <24 months
  • First relapse
  • Transformation to diffuse large B-cell lymphoma

Diffuse Large B-Cell Lymphoma

  • 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
  • Primary CNS lymphoma at diagnosis

High Grade B-Cell Lymphoma

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

Mantle Cell Lymphoma

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

Mature T-cell Lymphoma

  • CR1
  • First relapse

Other High-Risk Lymphomas

  • At diagnosis

Non-Hodgkin lymphoma transplant advances and outcomes data

Hodgkin Lymphoma

  • Primary induction failure
  • First relapse
  • CR2 or subsequent relapse

Hodgkin lymphoma transplant advances and outcomes data

Multiple Myeloma and Other Malignant Diseases


Multiple Myeloma

  • At diagnosis
  • At first progression

Multiple myeloma transplant advances and outcomes data

Germ Cell Tumors

  • Poor initial response
  • Short initial remission

Neuroblastoma

  • INSS stage 2 or 3 at diagnosis
    • MYCN amplification (>4x above reference)
  • INSS stage 4 at diagnosis
    • MYCN amplification (>4x above reference)
    • age >18 months at diagnosis
    • age 12-18 months with unfavorable characteristics
  • Metastatic disease at diagnosis
  • Progressive disease while on therapy or relapsed disease

Ewing Family of Tumors

  • Metastatic disease at diagnosis
  • First relapse or CR2

Medulloblastoma

  • First relapse or CR2

Hemoglobinopathies


Sickle Cell Disease (SCD)

  • Children with available matched sibling donor should be referred at diagnosis
  • 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
    • ≥ 2 episodes of acute chest syndrome/2-year period [or] ‘Recurrent’ acute chest syndrome
    • Regular red blood cell transfusion therapy (8 or more per year)
    • Tricuspid value regurgitant jet (TRJ) velocity ≥2.7 m/sec
    • Chronic pain ≥ 6 months (leg ulcers, avascular necrosis)
    • Abnormal transcranial Doppler (TCD) velocity of ≥ 200 cm/sec or > 185 cm/sec with intracranial vasculopathy
    • Silent cerebral infarct
    • ≥3 severe vaso-occlusive pain crises per 2-year period

Sickle cell disease transplant advances and outcomes data

Transfusion-Dependent Thalassemias

  • At diagnosis

Thalassemia transplant advances and outcomes data

Other 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 or if detected on newborn screening

Inherited metabolic disorders transplant outcomes data

Hemophagocytic Lymphohistiocytosis (HLH)

  • At diagnosis

Severe Aplastic Anemia and Other Marrow Failure Syndromes

(including Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome and others)
  • At diagnosis

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) or/and 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)

References

  1. Lee, SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13): 4576-4583. Access
  2. Pidala J, Lee SJ, Ahn KW, et al. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood. 2014:124(16):2596-2606. Access