Q501 – 558: Multiple Myeloma / Plasma Cell Disorder

One kind of white blood cell, the plasma cell (also called plasma B cells, plasmocytes, or effector B cells), produces proteins called antibodies or immunoglobulins (Igs) that are part of our defense system against foreign substances (called antigens). Antibodies are produced in response to such things as viruses, bacteria, and other infectious agents.

Multiple myeloma is a cancer that leads to the proliferation of malignant plasma cells (myeloma cells). Myeloma cells usually proliferate in the bone marrow. When myeloma cells grow into isolated masses in other sites, these masses are called plasmacytomas. Health problems caused by multiple myeloma can affect the bones, immune system, kidneys, and red blood cell count.

The immunoglobulins (antibodies) produced by healthy plasma cells are composed of pairs of heavy chains and light chains (see graphic below). Healthy plasma cells create many different kinds of immunoglobulins that are classified by their heavy chain type into five categories (IgG, IgA, IgM, IgD, or IgE). The light chain types are designated kappa (κ) or lambda (λ). The whole Ig molecule is then labeled IgG kappa, IgG lambda, IgA kappa, IgA lambda, etc. These protein levels can be measured in blood serum and/or urine.

Structure of an Immunoglobulin (Antibody)

Secretory Multiple Myeloma
Healthy plasma cells make immunoglobulins (antibodies) of all types. With the proliferation of malignant plasma cells, the level of one immunoglobulin type increases in the blood and/or urine. This abnormal immunoglobulin type is called the monoclonal immunoglobulin, monoclonal protein (M-protein/M-spike/M-component), or paraprotein. In most cases, the normal immunoglobulins are reciprocally depressed. Patients with this condition are said to have secretory myeloma.

Some myeloma patients make only an excess of the light chain portion of the immunoglobulin molecule (i.e., only monoclonal kappa or lambda light chains). The light chain is also called Bence Jones protein. In most patients whose myeloma cells only make light chains, this paraprotein may not be detectable in the blood, but only in the urine. These patients are said to have light-chain-only disease. Ninety-seven percent of patients diagnosed with multiple myeloma have a detectable paraprotein in the blood serum and/or urine.

Table 1. Distribution of Monoclonal Proteins in Secretory Multiple Myeloma¹²

Monoclonal Proteins at Diagnosis	Percent
Source of monoclonal proteins
Serum monoclonal proteins	80%
Urine monoclonal proteins	75%
Type of monoclonal proteins
IgG	50-54%
IgA	20%
Monoclonal light chain (light-chain-only disease)	20%
IgD	2%

¹ Kyle RA, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21-33.

² International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haem. 2003;121(5):749-57.

Nonsecretory Multiple Myeloma
In some myeloma patients, the malignant plasma cells do not produce an excess of the heavy chain or light chain portion of the immunoglobulin molecule; therefore, a paraprotein is not detectable in the serum or urine. These patients are said to have nonsecretory myeloma (i.e., the absence of a paraprotein on immunofixation). Immunofixation detects the specific immunoglobulins after separating the proteins into bands on an electrophoresis gel. Nonsecretory myeloma accounts for 3% of myeloma cases.

Amyloidosis
Amyloidosis is a disease in which abnormally folded proteins build up in different tissues of the body. In the most common amyloidosis, AL amyloidosis, the abnormally folded protein is the light chain component of an immunoglobulin. These light chains may build up in a variety of tissues, but the most common sites of build-up are the heart, kidneys, liver and nerves. According to the Amyloidosis Foundation, AL Amyloidosis is a relatively rare disorder, with 1200-3200 new cases reported each year in the United States. The disease mostly impacts men and people over 40.³

³ Amyloidosis Foundation. Amyloidosis – Primary AL. 15 Apr. 2013. Accessed at: http://www.amyloidosis.org/TreatmentInformation/primaryAL.html
Accessibility verified on October 21, 2013.

Question 1: Date of diagnosis of primary disease for infusion

Report the diagnosis date as the first date when all diagnostic criteria for the multiple myeloma / PCD subtype is met. Refer to the criteria listed below for symptomatic multiple myeloma. For other multiple myeloma / PCD subtypes, refer to the guidelines listed in the Disease Assessments at Diagnosis section of the PCD Pre-Infusion manual.

If the diagnosis was determined at an outside center, and no documentation of a pathological or laboratory assessment is available, the dictated date of diagnosis within a physician note may be reported. Do not report the date symptoms first appeared.

If the exact diagnosis date is not known, use the process described in General Instructions, Guidelines for Completing Forms

Multiple Myeloma (symptomatic)⁴
Diagnostic criteria for symptomatic multiple myeloma require clonal bone marrow plasma cells in ≥ 10% or biopsy proven bony or extramedullary plasmacytoma and any one or more of the following myeloma-defining events:

1. Evidence of end organ damage (i.e., CRAB features) that can be attributed to the underlying plasma cell proliferative disorder, specifically:

• Hypercalcemia: serum calcium >1 mg/dL (> 0.25 mmol/L) higher than the ULN or > 11 mg/dL (> 2.75 mmol/L)
• Renal insufficiency: creatinine clearance < 40 ml/min or serum creatinine > 2 mg/dL (> 177 μmol/L)
• Anemia: hemoglobin > 2 g/dL (> 20 g/L) below the LLN or a hemoglobin < 10 g/dL (< 100 g/L)
• Bone lesions: one or more osteolytic lesions on skeletal x-ray, CT or PET-CT
  

2. Any one or more of the following biomarkers of malignancy:

• Clonal bone marrow plasma cell percentage ≥ 60%
• Involved : uninvolved serum free light chain ratio ≥ 100
• > 1 focal lesions on MRI studies (each lesion must be ≥ 5 mm in size)
  

⁴ (2015, October 29). International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. Retrieved February 15, 2017, from http://imwg.myeloma.org/international-myeloma-working-group-imwg-criteria-for-the-diagnosis-of-multiple-myeloma/

*Submitting Disease Classification Documentation
If the primary disease for infusion is MGRS, CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 501 – 507: Specify the multiple myeloma / plasma cell disorder (PCD) classification

CIBMTR captures the classification of multiple myeloma and PCDs based on the World Health Organization (WHO) 2022, but also recognizes International Consensus Classification (ICC) 2022 and those classifications are also included, when applicable. Indicate the multiple myeloma / plasma cell disorder (PCD) disease classification for infusion. If the subtype is not listed, report as Other plasma cell disorder and specify the reported disease.

Plasma Cell Disorders and Characteristics

Multiple Myeloma (symptomatic)⁴
Diagnostic criteria for symptomatic multiple myeloma requires clonal bone marrow plasma cells in ≥ 10% or biopsy proven bony or extramedullary plasmacytoma and any one or more of the following myeloma-defining events:

1. Evidence of end organ damage (i.e., CRAB features) that can be attributed to the underlying plasma cell proliferative disorder, specifically:

• Hypercalcemia: serum calcium >1 mg/dL (> 0.25 mmol/L) higher than the ULN or > 11 mg/dL (> 2.75 mmol/L)
• Renal insufficiency: creatinine clearance < 40 ml/min or serum creat >2 mg/dL (> 177 μmol/L)
• Anemia: hemoglobin > 2 g/dL (> 20 g/L) below the LLN or a hemoglobin <10 g/dL (< 100 g/dL)
• Bone lesions: one or more osteolytic lesions on skeletal x-ray, CT or PET-CT

2. Any one or more of the following biomarkers of malignancy:

• Clonal bone marrow plasma percentage ≥ 60%
• Involved : uninvolved serum free light chain ratio ≥ 100
• > 1 focal lesion on MRI studies (each lesion must be ≥ 5 mm in size)

⁴ (2015, October 29). International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma. Retrieved February 15, 2017, from http://imwg.myeloma.org/international-myeloma-working-group-imwg-criteria-for-the-diagnosis-of-multiple-myeloma/

Plasma Cell Leukemia

• Peripheral blood absolute plasma cell count of at least 2.0 × 10⁹/L (2,000 cells/mm³)
• ≥ 20% plasma cells in the peripheral differential white blood cell count.⁵
  

*Multiple Plasmacytomas
If the recipient has greater than one plasmacytoma but has not been diagnosed with another plasma cell disorder, select Other plasma cell disorder and specify how many plasmacytomas are present and if each is bone derived or extramedullary.

Plasmacytoma (in absence of bone marrow findings diagnostic for multiple myeloma or plasma cell leukemia)

• Extraosseous plasmacytoma
  • Extramedullary tumor of clonal plasma cells
  • Normal bone marrow
  • Normal skeletal survey
  • No related organ or tissue impairment (end organ damage including bone lesions)
• Solitary plasmacytoma of bone
  • Single area of bone destruction due to clonal plasma cells
  • Bone marrow not consistent with multiple myeloma
  • Normal skeletal survey (and MRI of spine and pelvis if done)
  • No related organ or tissue impairment (no end organ damage other than solitary bone lesion)⁵

⁵ The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma, and related disorders: a report of the international myeloma working group. Brit J Haematol. 2003;121(5):749-57.

Immuno-globulin-related (AL) amyloidosis
Immuno-globulin-related (AL) amyloidosis is the buildup of abnormally folded proteins in various tissues of the body. Affected tissues may include the kidneys, heart, liver, gastrointestinal tract, etc. In the most common type of Immuno-globulin-related (AL) amyloidosis, “AL amyloidosis,” light chains from antibodies function as the amyloid protein, building up within organs and disrupting organ function. Serum and urine tests are useful for evaluating amyloidosis, but a tissue biopsy is the best way to diagnose the condition.

POEMS Syndrome
POEMS syndrome is poorly understood, but generally refers to P*olyneuropathy, *O*rganomegaly, *E*ndocrinopathy, *M protein, and *S*kin changes. Diagnosis may be made using the presence of the major criteria and one minor criteria below

• Major Criteria (both of the following)
  • Polyneuropathy
  • Monoclonal plasmaproliferative disorder
• Minor Criteria (at least one of the following)
  • Sclerotic bone lesions⁶
  • Castleman disease⁶
  • Organomegaly (splenomegaly, hepatomegaly, lymphadenopathy)
  • Edema (edema, pleural effusion, or ascites)
  • Endocrinopathy (adrenal, thyroid⁷, pituitary, gonadal, parathyroid, pancreatic⁷)
  • Skin changes (hyperpigmentation, hypertrichosis, plethora, hemangiomata, white nails)
  • Papilledema

⁶ Osteosclerotic lesion or Castleman disease is usually present.

⁷ Because of the high prevalence of diabetes mellitus and thyroid abnormalities, this diagnosis alone is not sufficient to meet this minor criterion. Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood. 2003;101(7):2496-506.

Monoclonal gammopathy of renal significance (MGRS)
Monoclonal gammopathy of renal significance (MGRS), similar to monoclonal gammopathies of unknown significance (MGUS), represent a group of disorders in which a monoclonal immunoglobulin is secreted by a non-malignant ore pre-malignant B cell or plasma cell clone. MGRS is characterized by demonstrated renal damage attributable to the underlying M-protein, unlike MGUS recipients who exhibit no end-organ damage. By definition and classification criteria, these disorders differ from symptomatic myeloma and lymphoproliferative disorders. Recipients diagnosed with MGRS are at risk of developing progressive renal disease in addition to other hematologic disorders.⁸

⁸ The Hematologist: ASH News and Reports. Monoclonal Gammopathy of Renal Significance. 16 Oct. 2018. Accessed at: https://www.hematology.org/Thehematologist/Ask/9059.aspx Accessibility verified on November 4, 2019.

Specifying Disease Sub-Classification

Multiple myeloma

• If the recipient’s disease classification is one of the following listed below, specify heavy and / or light chain type, select all that apply. Only report more than one heavy and / or light chain if the recipient is diagnosed with bi-clonal multiple myeloma.
  • Multiple myeloma – IgG
  • Multiple myeloma – IgA
  • Multiple myeloma – IgD
  • Multiple myeloma – IgE
  • Multiple myeloma – IgM (not Waldenstrom macroglobulinemia)
  • Multiple myeloma – light chain only

Immuno-globulin-related (AL) amyloidosis

• Specify the amyloidosis classification as one of the following:
  • AL amyloidosis (light-chain amyloidosis): This is the most common type of amyloidosis where the abnormally folded protein is the light chain component of an immunoglobulin. Misfolded proteins can deposit in the nervous system, heart, kidneys, or digestive tract; however, they can often affect more than one organ.9
  • AH amyloidosis (heavy-chain amyloidosis): This is a rare type of amyloidosis where the abnormally folded protein is the heavy chain component of an immunoglobulin.⁹
  • AHL amyloidosis (heavy- and light-chain amyloidosis): This is a rare type of amyloidosis where the abnormally folded protein is composed of fragments of both the Ig heavy chain and light chain.¹⁰

⁹ “AL Amyloidosis.” Amyloidosis Foundation, http://amyloidosis.org/facts/al/.

¹⁰ Nasr, S. H. (2013). The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis. Kidney International, 83(3), 463–470. https://doi.org/10.1038/ki.2012.414

*Light and Heavy Chain Deposition Disease
If ‘light and heavy chain deposition disease’ is the MIDD disease classification, select both Light chain deposition disease and Heavy chain deposition disease.

Monoclonal gammopathy of renal significance (MGRS)

• Specify the MGRS classification.
  • If the MGRS classification is Monoclonal immunoglobulin deposition disease (MIDD), then the MIDD subtype must be specified.

*Multiple Plasmacytomas
If the recipient has greater than one plasmacytoma but has not been diagnosed with another plasma cell disorder, select Other plasma cell disorder and specify how many plasmacytomas are present and if each is bone derived or extramedullary.

Plasmacytoma

• Specify the type of plasmacytoma as Extraosseous plasmacytoma (i.e., extramedullary) or Solitary plasmacytoma of bone (i.e., bone derived). Refer to the Plasma Cell Characteristics above for additional information regarding the characteristics of each type.
  

Other plasma cell disorder

• If the recipient’s disease classification is not listed, specify the disease.
  

Question 508: Did the recipient have a preceding or concurrent plasma cell disorder?

Indicate if the recipient had a concurrent or preceding plasma cell disorder. Many recipients progress to symptomatic myeloma from a preceding condition or have concurrent plasma cell disorder, such as amyloidosis.

• Example 1 If a recipient has smoldering myeloma (asymptomatic) and then develops symptomatic multiple myeloma, Multiple myeloma should be reported as the primary diagnosis and Smoldering myeloma should be reported as the preceding / concurrent disorder.
• Example 2: If a recipient has smoldering myeloma (asymptomatic) and amyloidosis, Immuno-globulin-related (AL) amyloidosis should be reported as the primary diagnosis and Smoldering myeloma should be reported as the preceding / concurrent disorder.
• Example 3: If the recipient has symptomatic multiple myeloma and amyloidosis, Multiple myeloma should be reported as the primary diagnosis and Immuno-globulin-related (AL) amyloidosis should be reported as the preceding / concurrent disorder.

*Reporting More Than One Concurrent or Preceding Disorder
Copy Specify preceding / concurrent disorder and Date of diagnosis of preceding / concurrent disorder questions to report more than one concurrent or preceding disorder.

Questions 509 – 510: Specify preceding / concurrent disorder

Indicate the preceding or concurrent disorder. See the Plasma Cell Characteristics information above for descriptions of diseases and the previous question for examples of situations with preceding or concurrent disorders. If the recipient has a preceding or concurrent plasma cell disorder that is not listed, select Other plasma cell disorder (PCD) and specify the type.

Question 511: Date of diagnosis or preceding / concurrent disorder

Report the date the recipient was first diagnosed with the preceding or concurrent plasma cell disorder. Enter the date the blood/urine was collected for the laboratory evaluations (e.g., serum/urine protein electrophoresis (SPEP / UPEP, respectively), or serum / urine immunofixation) or enter the date of the first pathological diagnosis (e.g., bone marrow biopsy, plasmacytoma, tissue). Enter the date the sample was collected for examination.

If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.

*Assessments at Diagnosis of PCD
Report laboratory results closest to the diagnosis date and prior to the start of first treatment of the primary disease for which the infusion is being performed.

Questions 512 – 521: Laboratory studies at diagnosis for the disease for which the infusion is being done_ (check all that apply)_

This section is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion.

These questions are intended to determine the clinical status of the recipient and disease staging of the primary disease for infusion at diagnosis. Select all lab values known at diagnosis. All values reported must reflect testing performed prior to the start of treatment. If labs were assessed multiple times prior to starting treatment, report the values closest to the diagnosis date.

• Serum calcium: Calcium is an essential mineral for bodily functions. It is assessed to identify or monitor certain diseases (including bone, kidney, and parathyroid diseases). Hypercalcemia is common in recipients with multiple myeloma as it can cause extra bone resorption, resulting in release of calcium in excessive amounts. If known, specify the value and units of measurement as documented on the lab report.
• Serum creatinine: Creatinine is a normal metabolic waste that is primarily filtered from the blood by the kidneys and then excreted in the urine. Since it is generally produced at a constant rate, the clearance rate and the serum level are widely used as indicators of kidney function. If known, specify the value and units of measurement as documented on the lab report.
• Hemoglobin: Hemoglobin is a molecule in red blood cells that delivers oxygen to tissues throughout the body. A low hemoglobin count is considered “anemia” and blood transfusions, or growth factors may be required to increase the hemoglobin level. If known, specify the value and units of measurement as documented on the lab report.
• LDH: Lactate dehydrogenase is an enzyme found in the cytoplasm of almost all tissues, which converts L-lactate into pyruvate, or pyruvate into L-lactate depending on the oxygen level. For some diseases, high levels indicate active disease (e.g., lymphoma and multiple myeloma). If known, specify the value, units of measurement, and the upper limit of normal as documented on the lab report.
• Serum albumin: Serum albumin is a protein found in the blood. Levels are most often reported on a chemistry panel but may occasionally be found in a separate liver function test report. If known, specify the value and units of measurement as documented on the lab report.
• Serum β2-microglobulin: Serum β2 microglobulin is a protein found in the blood and urine and can also be found on the surface of various cells. If known, specify the value and units of measurement as documented on the lab report.
• Plasma cells in peripheral blood by morphologic assessment: Plasma cells are not typically detected in the peripheral blood; however, can appear for various reasons, including infection, certain diseases, like multiple myeloma, post-immunization. If known, report the percentage of plasma cells detected in the blood by morphologic assessment and / or the absolute number as documented and units of measurement as on the lab report.
  • If a differential was performed and the percentage of plasma cells are not listed, report 0%.
  • If only the percentage of plasma cells is available, the absolute number of plasma cells can be determined by multiplying the percentage of plasma cells by the white blood count (WBC).

If the lab values listed above were not assessed at diagnosis or unknown if completed, select None.

Questions 522 – 523: Plasma cells in peripheral blood by flow cytometry

This question is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion.

Indicate if plasma cells in the peripheral blood by flow cytometry was known at the time of diagnosis of the primary disease for infusion. If Known, report the percentage of plasma cells detected in the blood by flow cytometry documented on the flow cytometry report.

If this lab was assessed multiple times prior to starting treatment, report the values closest to the diagnosis date.

Question 524: I.S.S. stage (at diagnosis)

This question is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion and none of the components needed to calculate the I.S.S. staging were reported elsewhere on the Disease Classification (2402) form.

Report the recipient’s I.S.S. stage of myeloma at diagnosis.

Table 2. I.S.S. Staging System for Multiple Myeloma¹¹

Stage	Description
Stage 1	Serum β2-microglobulin < 3.5 mg/L and serum albumin ≥ 3.5 g/dL
Stage 2	Not fitting stage 1 or 3; serum β2-microglobulin < 3.5 mg/L and serum albumin < 3.5 g/dL OR Serum β2-microglobulin 3.5 to <5.5 mg/dL irrespective of serum albumin level
Stage 3	Serum β2-microglobulin ≥ 5.5 mg/L irrespective of serum albumin level

¹¹ 11 Greipp, P. R., San Miguel, J., Durie, B. G., Crowley, J. J., Barlogie, B., Bladé, J., … & Westin, J. (2005). International staging system for multiple myeloma. Journal of Clinical Oncology, 23(15), 3412-3420.

Question 525: R – I.S.S. stage (at diagnosis)

This question is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion and none of the components needed to calculate the R-I.S.S. staging is not reported elsewhere on the Disease Classification (2402) form.

The Revised International Staging System (R-I.S.S.) includes variables included in the original ISS (serum beta-2 microglobulin and serum albumin), while also including the additional prognostic information obtained from serum LDH and high-risk chromosomal abnormalities detected by interphase fluorescent in situ hybridization (iFISH) after CD138 plasma cell purification.¹² High risk chromosomal abnormalities identified by iFISH include:

• Deletion 17p / 17p-
• t(4;14)
• t(14;16)
  

Report the recipient’s R-I.S.S. stage of myeloma at diagnosis.

Table 3. R-I.S.S. Staging System for Multiple Myeloma¹²

Stage 1	Requires all the following: I.S.S. stage 1 No high-risk cytogenetic abnormalities by FISH (deletion 17p / 17p-, t(4;14), t(14;16)) Normal LDH levels
Stage 2	Not R-ISS stage I or III
Stage 3	Requires all the following: I.S.S. stage 3 High-risk cytogenetic abnormalities by FISH (deletion 17p / 17p-, t(4;14), t(14;16)) or high LDH levels

¹² Palumbo, A. et al (2015). Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 33(26), 2863-9. doi: 10.1200/JCO.2015.61.

Questions 526 – 527: Durie-Salmon stage and sub classification (at diagnosis)

This question is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion, the I.S.S. stage is not reported and none of the components needed to calculate the Durie-Salmon staging is not reported elsewhere on the Disease Classification (2402) form.

Indicate Durie-Salmon stage and sub classification at diagnosis. If the Durie-Salmon stage and / or sub classification is not documented in the medical record, use the table below to determine the appropriate stage.

If the Durie-Salmon stage is unknown and cannot be determined using the table below, select Unknown.

Table 4. Durie-Salmon Staging System for Multiple Myeloma¹³

Stage	Criteria
I	All of the following: • Hemoglobin > 10 g/dL • Serum calcium normal (< 10.5 mg/dL) • On radiograph, normal bone structure or solitary bone plasmacytoma only • Low M-component production rate (IgG < 5 g/dL, IgA < 3 g/dL), Urinary light chain M-component on electrophoresis (< 4 g/24 hr)
II	Fitting neither stage I nor stage III
III	One or more of the following: • Hemoglobin < 8.5 g/dL • Serum calcium > 12 mg/dL • Advanced lytic bone lesions (three or more lytic lesions) • High M-component product rate (IgG > 7 g/dL, IgA > 5 g/dL), Urinary light chain M-component on electrophoresis (> 12 g/24 hr)
Sub-classification	(either A or B) A: Relatively normal renal function (serum creatinine < 2.0 mg/dL) B: Abnormal renal function (serum creatinine ≥ 2.0 mg/dL)

¹³ Adapted from Durie BG, Salmon SE: A clinical staging system for multiple myeloma: Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36:842-54.

Question 528: Were cytogenetics tested (karyotyping or FISH)? (at diagnosis)

This question is only enabled if this is the first CIBMTR reported infusion of the primary disease for infusion.

Cytogenetic analysis is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of a known chromosomal abnormality which reflects the recipient’s disease.

Testing methods you may see include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.

Indicate whether cytogenetic studies were performed at diagnosis. If cytogenetic studies were performed at diagnosis, check Yes. If cytogenetic studies were not obtained at diagnosis, or it is not known whether chromosome studies were performed, indicate No or Unknown, respectively.

Questions 529 – 530: Were cytogenetics tested via FISH? (at diagnosis)

Specify if FISH studies were performed at diagnosis. If Yes, indicate whether clonal abnormalities were detected. If FISH studies were not performed at diagnosis, FISH samples were inadequate, or the results ‘failed,’ report No.

If it is unknown if performed, report Unknown.

Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.

!International System for Human Cytogenetic (ISCN) Compatible String
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled and cannot be answered at this time.

*Submitting FISH Documentation
CIBMTR strongly encourages attaching the FISH report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 531 – 533: Specify FISH abnormalities (at diagnosis)

Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select all cytogenetic abnormalities identified by FISH assessments at diagnosis.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

Questions 534 – 535: Were cytogenetics tested via karyotyping? (at diagnosis)

Specify if karyotyping studies were performed at diagnosis. If Yes, indicate if abnormalities were detected. If the karyotype failed or insufficient growth, select No evaluable metaphases.

If karyotyping studies were not performed at diagnosis or is unknown if performed, report No or Unknown, respectively.

*Submitting Karyotype Documentation
CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 536 – 538: Specify karyotype abnormalities (at diagnosis)

Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select all cytogenetic abnormalities identified by karyotype at diagnosis.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

**Last Evaluation Assessments *
Assessments performed at diagnosis (for the first infusion) and last evaluation (for subsequent infusions) questions ask about testing performed at different time points prior to infusion. For reporting purposes, the last evaluation time point is defined as the most recent testing performed during the recipient’s work-up for infusion. Assessments performed during the last line of therapy or after the last line of therapy may be reported. If multiple assessments were performed, report the most recent. If additional therapy was given after the last assessment, do not report the test.

Questions 539 – 543: Laboratory studies at last evaluation prior to the start of the preparative regimen (for subsequent infusion) (check all that apply)

This question is only enabled if this is a subsequent infusion reported to CIBMTR for the same primary disease for infusion.

These questions are intended to determine the clinical status of the recipient and disease staging of the primary disease at the last evaluation prior to the subsequent infusion.

Select all lab values known at the last evaluation. Do not report any values from the initial diagnosis. If labs were assessed multiple times, report the most recent values prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given). Laboratory values obtained on the first date of the preparative regimen / lymphodepleting therapy may be reported as long as the sample was collected before any administration of systemic therapy or radiation.

• Serum creatinine: Creatinine is a normal metabolic waste that is primarily filtered from the blood by the kidneys and then excreted in the urine. Since it is generally produced at a constant rate, the clearance rate and the serum level are widely used as indicators of kidney function. If known, specify the value and units of measurement as documented on the lab report.
• Hemoglobin: Hemoglobin is a molecule in red blood cells that delivers oxygen to tissues throughout the body. A low hemoglobin count is considered “anemia” and blood transfusions, or growth factors may be required to increase the hemoglobin level. If known, specify the value and units of measurement as documented on the lab report.
• Plasma cells in peripheral blood by morphologic assessment: Plasma cells are not typically detected in the peripheral blood; however, can appear for various reasons, including infection, certain diseases, like multiple myeloma, post-immunization. If known, report the percentage of plasma cells detected in the blood by morphologic assessment and / or the absolute number as documented and units of measurement as on the lab report.
  • If a differential was performed and the percentage of plasma cells are not listed, report 0%.
  • If only the percentage of plasma cells is available, the absolute number of plasma cells can be determined by multiplying the percentage of plasma cells by the white blood count (WBC).

If the labs values listed above were not assessed at the last evaluation or unknown if completed, select None.

Questions 544 – 545: Plasma cells in peripheral blood by flow cytometry

This question is only enabled if this is a subsequent infusion reported to CIBMTR for the same primary disease for infusion

Indicate if plasma cells in the peripheral blood by flow cytometry was known the last evaluation prior to the subsequent infusion. If Known, report the percentage of plasma cells detected in the blood by flow cytometry documented on the flow cytometry report.

If labs were assessed multiple times, report the most recent values prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given). Laboratory values obtained on the first date of the preparative regimen / lymphodepleting therapy may be reported as long as the sample was collected before any administration of systemic therapy or radiation.

Question 546: Were cytogenetics tested (karyotyping or FISH)? (for subsequent infusion, at last evaluation)

This question is only enabled if this is a subsequent infusion reported to CIBMTR for the same primary disease for infusion

Cytogenetic analysis is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of a known chromosomal abnormality which reflects the recipient’s disease.

Testing methods you may see include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see” Appendix C: Cytogenetics”:https://www.manula.com/manuals/cibmtr/fim/1/en/topic/appendix-c.

Indicate whether cytogenetic studies were performed at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given) for the subsequent infusion. If cytogenetic studies were performed, check Yes. If cytogenetic studies were not obtained, or it is not known whether chromosome studies were performed, indicate No.

Questions 547 – 548: Were cytogenetics tested via FISH? (for subsequent infusion, at last evaluation)

Specify if FISH studies were performed at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given) for the subsequent infusion. If Yes, indicate whether clonal abnormalities were detected. If FISH studies were not performed, FISH samples were inadequate, results ‘failed,’ or it is unknown if performed, report No.

Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.

!International System for Human Cytogenetic Nomenclature (ISCN) for FISH
The International System for Human Cytogenetic Nomenclature (ISCN) compatible string is disabled for FISH and cannot be answered at this time.

*Submitting FISH Documentation
CIBMTR strongly encourages attaching the FISH report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 549 – 551: Specify FISH results (for subsequent infusion, at last evaluation)

Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select all cytogenetic abnormalities identified by FISH assessments at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given) for the subsequent infusion.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

Questions 552 – 553: Were cytogenetics tested via karyotyping? (for subsequent infusion, at last evaluation)

Specify if karyotyping studies were performed at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given) for the subsequent infusion. If Yes, indicate if abnormalities were detected. If the karyotype failed, select No evaluable metaphases.

If karyotyping studies were not performed at the last evaluation or is unknown if performed, report No.

*Submitting Karyotype Documentation
CIBMTR strongly encourages attaching the karyotype report when abnormalities are identified. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide.

Questions 554 – 556: Specify karyotyping results (for subsequent infusion, at last evaluation)

Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.

If the ISCN compatible string is not reported, then select all cytogenetic abnormalities identified by karyotype at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if preparative regimen / lymphodepleting therapy was not given) for the subsequent infusion.

If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.

*Treatment Never Given for Myeloma
If treatment was never given, then report the disease status as No response (NR) / stable disease (SD) or Progressive disease (PD), depending on the scenario.

Question 557: What was the disease status? _(at infusion) _

This data field is intended to capture the pre-infusion disease status, based on clinical / hematologic assessments. Refer to the Multiple Myeloma Response Criteria section for multiple myeloma and solitary plasmacytoma disease status definitions and Plasma Cell Leukemia Response Criteria for plasma cell leukemia disease status definitions.

Report the disease status prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the recipient relapsed prior to the infusion and did not receive additional therapy following the relapse, select Relapse from CR (Rel) (untreated).

*Treatment Never Given for Amyloidosis
If treatment was never given, then report the disease status as No response (NR) / stable disease (SD) or Progressive disease (PD), depending on the scenario.

Question 558: Specify amyloidosis hematologic response (for Amyloid patients only) (at infusion)

This data field is intended to capture the pre-infusion disease status, based on clinical / hematologic assessments. Refer to the Amyloidosis Response Criteria section for disease status definitions.

Report the disease status prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).

If the recipient relapsed prior to the infusion and did not receive additional therapy following the relapse, select Relapse from CR (Rel) (untreated).

Section Updates:

Question Number	Date of Change	Add/Remove/Modify	Description	Reasoning (If applicable)
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