Shared clonal
            IGH
            rearrangement in BCP‐ALL occurring after CLL: pitfalls and implications for MRD monitoring

Abstract Although most multiple myeloma (MM) cases are characterized by the detection of a monoclonal immunoglobulin in the serum, about 15% of the patients present only immunoglobulin light chains, detected either in the urine or serum or both. These patients are designated as having light-chain (LC) MM. Using fiber-fluorescent in situ hybridization, and in contrast to patients and myeloma cell lines secreting heavy chains (who presented a legitimate functional IgH rearrangement in every case), LC MM never displayed a functional IgH recombination. Interestingly, most LC MM cases presented one IgH allele with a germline configuration (including the DJ region), the second allele being usually involved in an illegitimate recombination. Of note, most of these translocations occurred close to (or at) switch regions, even though in some cases, breakpoints involving nonswitch regions were observed. Thus, this study clearly showed that LC MM is due to the absence of legitimate IgH rearrangement at the DNA level, reflecting possible abnormalities in the IgH gene recombinations during B-cell maturation. Furthermore, it showed that this defect did not prevent the activation of the switch process because most of 14q32 translocations observed in LC MM occurred at switch regions.

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SOX11 expression as a MRD molecular marker for MCL in comparison with t(11;14) and IGH rearrangement

Medical Oncology ◽

10.1007/s12032-018-1111-x ◽

2018 ◽

Vol 35 (4) ◽

Cited By ~ 1

Author(s):

Małgorzata Szostakowska ◽

Michał Szymczyk ◽

Kalina Badowska ◽

Barbara Tudek ◽

Anna Fabisiewicz

Keyword(s):

Molecular Marker ◽

Sox11 Expression ◽

Igh Rearrangement

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The bcl-2/IgH rearrangement in a population of 204 healthy individuals: Occurrence, age and gender distribution, breakpoints, and detection method validity

Leukemia Research ◽

10.1016/j.leukres.2005.10.001 ◽

2006 ◽

Vol 30 (6) ◽

pp. 745-750 ◽

Cited By ~ 42

Author(s):

Christina Schmitt ◽

Brigitta Balogh ◽

Alexander Grundt ◽

Christian Buchholtz ◽

Albrecht Leo ◽

...

Keyword(s):

Detection Method ◽

Healthy Individuals ◽

Age And Gender ◽

Gender Distribution ◽

And Gender ◽

Igh Rearrangement

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High Frequency of Normal IgH Rearrangement in scid Mice

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1995.tb55814.x ◽

2008 ◽

Vol 764 (1) ◽

pp. 121-122

Author(s):

JACQUELINE PENNYCOOK ◽

AARON MARSHALL ◽

YENHUI CHANG ◽

ROBERT A. PHILLIPS ◽

GILLIAN E. WU

Keyword(s):

High Frequency ◽

Scid Mice ◽

Igh Rearrangement

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The Impact of a Reflex Testing Strategy for High Risk Chromosome 14 Abnormalities on FISH Laboratory Costs in Multiple Myeloma

Blood ◽

10.1182/blood-2019-132207 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3420-3420

Author(s):

Marta Isabel Pereira ◽

Gilberto Marques ◽

Joana Lima ◽

Artur Paiva ◽

Maria Leticia Ribeiro ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Prognostic Value ◽

A Priori ◽

Testing Strategy ◽

Chromosome 14 ◽

Reflex Testing ◽

The Mean ◽

Igh Rearrangement ◽

Mean Cost

Background: The detection of cytogenetic aberrations by fluorescence in situ hybridization (FISH) has prognostic value in multiple myeloma (MM), with the presence of del(17p), t(4;14) or t(14;16) currently defining high-risk chromosomal abnormalities (HR-CA) in the Revised International Staging System. Both t(4;14) and t(14;16) involve the IGH gene, and can be detected by FISH probes targeting IGH-rearrangements; these probes, in turn, can also detect other non-HR-CA involving this gene. Additionally, the interpretation of FISH probing is observer-dependent and influenced by the type of probe used. While dual-color dual-fusion (DC/DF) probes are more sensitive, break-apart (BA) probes are easier to interpret. Aims: We aim to analyze the economic outcome of switching from a DC/DF detection of HR-CA of chromosome 14 (Cr14) to a strategy of a BA detection of IGH rearrangements with reflex testing for t(4;14) and t(14;16) only in positive samples. Methods: We analyzed all FISH panels performed in our Lab for MM between June 1st 2015 and July 31st 2019. Until May 2016 we performed an a priori MM FISH panel consisting of probes for t(4;14), for del(17p), and for 1p/1q amplifications and deletions (Cohort 1); testing for t(14;16) was performed under request. From May 2016 to October 2017 we added a probe for t(14;16) to the routine panel (Cohort 2); during both periods, probing for IGH rearrangements was performed reflexively in the case of an inconclusive or otherwise uncertain t(4;14) and/or t(14;16) result. From November 2017 onwards we have probed for IGH rearrangements a priori, with reflex testing for t(4;14) and t(14;16) only in positive cases (IGH Cohort); testing for del(17p) and 1p/1q was unchanged throughout the timeframe and is not further analyzed in this study. We looked at the costs associated with the acquisition of the relevant FISH probes, as well as the number of hybridizations performed per patient, for each of the three strategies. Results: Over the time period under analysis we performed FISH panels on 450 MM patients (55% male); 21% of samples were from Cohort 1, 45% were from Cohort 2 and 34% were from the IGH Cohort. Only 28.9% of patients with a documented IGH rearrangement were positive for either t(4;14) or t(14;16). The mean cost per patient for IGH probes was 3.8±11.6 € in Cohort 1, 1.3±7.1 in Cohort 2 and 36.2±10.1 in the IGH Cohort (p<0.001). The mean cost for t(4;14) probes was 44.1±0, 44.1±0 and 22.0±22.1 €, respectively (p<0.001), and the mean cost for t(14;16) probes was 3.2±9.9, 31.2±8.5 and 16.3±16.8 €, respectively (p<0.001). Overall, the mean cost per patient for all three probes was 51.1±18.7, 76.6±9.5 and 74.5±33.3 €, respectively (p<0.001 for the pre- and post-t(14;16) comparison; and p=NS for the pre- and post-IGH comparison). The mean number of hybridizations performed per patient was 1.0±0.2 prior to the introduction of a priori IGH testing, and 1.4±0.5 in the IGH Cohort (p<0.001). Discussion: We found that the addition of routine testing for t(14;16) increased the mean cost of probes per patient by nearly 50% (from approximately 50€ to 75€ - US$55-85), while the switch to a priori testing for IGH rearrangements with reflex probing for the translocations did not increase costs with FISH probes, as the overall higher number of tests performed was balanced by the lower cost of the BA probe compared to the DC/DF probes, as well as a reduction in DC/DF probe consumption. On the other hand, after the switch, the number of hybridizations performed per patient increased 40%, corresponding to an increase in 40% in both laboratory technician and pathologist man-hours, and ancillary (non-probe) reagents spent. Less than two-thirds of patients with an IGH-rearrangement were positive for one of the two HR-CA of Cr14. This reflex testing strategy, therefore, has the clinical benefit of identifying patients for probing for additional Cr14 translocations of putative prognostic value, such as t(11;14). Conclusions: We found that this reflex testing strategy was associated with a 40% increase in non-probe reagents and in technician man-hours, but no significant impact in probe costs. This must be weighed against the potential clinical and scientific gains from the detection of additional Cr14 aberrations with thus-far uncertain or untested prognostic value. Disclosures No relevant conflicts of interest to declare.

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Comparison of Bone Marrow Biopsy, Flow Cytometry and PCR Assays To Detect Bone Marrow Involvement in B-Cell Non-Hodgkin Lymphomas.

Blood ◽

10.1182/blood.v106.11.4670.4670 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4670-4670

Author(s):

Giovanni Carulli ◽

Sara Galimberti ◽

Giuseppina Bianchi ◽

Alessandra Zucca ◽

Enrico Orciuolo ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

B Cell ◽

Bone Marrow Biopsy ◽

Gold Standard ◽

Residual Disease ◽

Bone Marrow Involvement ◽

False Negative ◽

Integrated Approach ◽

Igh Rearrangement

Abstract Bone marrow biopsy, (BMB) is essential to detect bone marrow (BM) infiltration in B-cell non-Hodgkin lymphomas (NHLs). Flow cytometry (FC) and PCR for clonal IgH rearrangement are considered as ancillary methods, but there is increasing evidence for their clinical usefulness. Observations dealing with combined use of the three methods still are lacking. Thus we carried out a retrospective study about the usefulness of an integrated approach to detect BM infiltration in NHLs. 193 patients suffering from NHLs (79 at presentation, 114 after chemotherapy alone or with: Rituximab, Campath-1, autologous BM transplantation), who had undergone simultaneous execution of BMB, and FC, and PCR from the myeloaspirate on the same iliac crest, were evaluated. BMB was carried out according to standard methods (infiltration pattern and immunohistochemistry). FC was performed using three-color staining, including CD45, to identify: κ/λ ratio, specific phenotype for CLL, MCL and HCL. PCR included identification of IgH rearrangement (CDR3 and VH families), BCL-1/JH translocation for MCL and BCL-2/JH translocation for follicular lymphoma. BMB, FC and PCR agreed in 142 cases and showed infiltration in 74 and lack of infiltration in 68. Cases at presentation were characterized by higher percentages of concordance than cases during the post-chemotherapy (84,8% vs 65.6%). Discrepant results were obtained in 51 cases (26.4%), 13 at presentation and 38 after treatment. In 17 specimens (8.8% of all cases, 33.3% of discordant cases), BM infiltration was detected only by PCR. In 12 of these samples (3 untreated and 14 treated) small B-cell percentages (0.50 ± 0.72, mean ± SD; range 0.02–3.00%) were present at FC. The remaining 5 cases (2.6%) were characterized by a lack of surface Ig expression and absence of specific phenotype: BMB was negative but IgH was clonal. 2 other cases with lack of surface Ig expression (for 7 cases in total, 3.6%), BMB-/PCR- were identified. Conversely, in 10 samples (5.2% of all cases, 19.6% of discordant specimens) PCR failed to detect BM infiltration, which was demonstrated by both FC and BMB. These specimens were characterized by high B-cell percentages (7 ± 8.25, mean ± SD; range 0.3–26.0%) and were obtained from 5 untreated and 5 treated patients. The remaining discordant cases were: 7 treated cases with BMB+/PCR+ and FC-; 6 cases (3 treated and 3 untreated) with FC+ and BMB-/PCR-; 3 treated cases with BMB- and FC+/PCR+; 3 cases (1 untreated and 2 treated) with BMB+ and FC-/PCR-. In the 3 treated cases with lack of amplification by PCR, the following results were observed: FC+/BMB+ in 1 case; FC-/BMB- in the remaining 2. Our data show that no single method is able to identify all cases of BM involvement in NHLs. BMB is actually considered the gold standard, however the combination of the three assays can increase the yields of detection of minimal residual disease. In fact, considering the three assays together as gold standard, BMB alone has a sensibility of 82.1%, a specificity of 96,3%, with 1.6% of false positive but 10.4% of false negative. The PCR can increase the sensibility and FC can than be considered as a valid confirmation assay, able to solve the cases when BMB and PCR show discrepancy. To conclude, the three assays are necessary to evaluate BM infiltration in NHLs, because BMB alone underestimate the BM involvement, especially following treatment.

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Detection of Clonality in Lymphoproliferations Using PCR of the Antigen Receptor Genes: Does Size Matter?.

Blood ◽

10.1182/blood.v108.11.4622.4622 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4622-4622

Author(s):

Paul G. Rothberg ◽

Roberto L. Vargas ◽

Raymond E. Felgar ◽

Susan L. Polochock ◽

Sharon D. Frazier

Keyword(s):

Cell Lymphoma ◽

Antigen Receptor ◽

B Cell Lymphoma ◽

Pcr Primers ◽

Convincing Evidence ◽

Low Grade ◽

Marginal Cell ◽

Igh Rearrangement ◽

Size Limits ◽

Size Matter

Abstract A biopsy of a nasal mass was received from another institution for a hematopathology consultation. The specimen had morphologic and immunostaining features consistent with a B-cell lymphoma, histologically low-grade, and suggestive for an extranodal marginal cell lymphoma of mucosa associated lymphoid tissue (MALT) type. We used PCR of the IgH gene to evaluate clonality on DNA derived from this specimen. The primers were from the BIOMED-2 report (van Dongen et al. 2003, Leukemia17:2257) and the amplicons were subjected to heteroduplex formation prior to PAGE. A homoduplex of approximately 140 bp was obtained reproducibly from the FR2 and JH primers, which is below the usually acceptable size limits of 250–295 bps. No homoduplex was obtained using FR3 and JH primers. We sequenced the FR2/JH amplicon using the PCR primers as sequencing primers. The amplicon was 137 bps, with 92 bps between the primers. After the upstream VH3 FR2 primer there were approximately 25 bps from the FR2 region of several members of the VH3 family, with VH3-49 (allele *03) being the best match. Adjacent to the downstream consensus JH primer there were approximately 30 bp from the J6 segment. Between the identifiable sequences there were 37 bp that we could not identify. Blast searches turned up several matches of 18 bp, but nothing that gave convincing evidence for its origin. We interpret these results as indicating a clonal IgH rearrangement followed by a deletion that removed most of the downstream portion of the V segment, including the FR3 region. It is likely that the 37 bp in between the identified IgH segments consists of randomly inserted nucleotides and IgH sequence that has been somatically mutated beyond recognition, although other interpretations are possible. However, the amplicon does appear to be derived from an IgH rearrangement, which is consistent with derivation from a monoclonal population of B-lymphocytes. This work illustrates that DNA fragments outside of the size range expected from PCR of the antigen receptor genes may still be consistent with a monoclonal result. Thus, this type of result should not be dismissed, but should be subjected to further analysis.

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Fluorescence In Situ Hybridization Studies in 22 Cases of Plasma Cell Leukemia.

Blood ◽

10.1182/blood.v108.11.4461.4461 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4461-4461

Author(s):

Jianyong Li ◽

Wei Xu ◽

Lijuan Chen ◽

Yu Zhu ◽

Jinlan Pan ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Plasma Cell ◽

Cell Leukemia ◽

Molecular Cytogenetic ◽

Cytogenetic Aberrations ◽

Plasma Cell Disorder ◽

Igh Rearrangement ◽

Cell Disorder

Abstract Background Plasma cell leukemia (PCL) is a rare malignant plasma cell disorder that usually carries an aggressive course with a rapidly fatal outcome. Cytogenetic studies performed on plasma cell disorder are scarce and difficult because of the low proliferation rate of plasma cells. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical and structural chromosomal changes in PCL. Methods Interphase FISH (I-FISH) and two different specific probes for the regions containing 13q14.3 (D13S319) or 14q32 (IGHC/IGHV) were used to detect 13q14 deletion [del(13q14)] or IgH rearrangement in 22 PCL patients. For patients with IgH rearrangement, probes for IgH(JH) and 11q13 (CCND1) or 4p16 (FGFR3) were used to detect t(11;14)(q13;q32) or t(4;14)(p16;q32). Results Molecular cytogenetic aberrations were found in 19 of 22 (86.4%) PCL patients. Del(13q14) was detected in 13 cases (59.1%), and IgH rearrangement in 17 (77.3%) patients including 7 with t(11;14) and 3 with t(4;14). 14q32 rearrangement and 13q14 deletion were found concurrently in 11 cases (50%). Conclusions Chromosomal abnormalities are frequent in PCL. The most frequent aberrations among the cases was the 14q32 rearrangement and 13q14 deletion. I-FISH technique is useful to detect molecular cytogenetic aberrations and should be used in the routine evaluation of PCL.

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Examination of Genetic Aberrations in Chlamydophila Psittaci negative MALT Lymphomas of the Ocular Adnexa

Blood ◽

10.1182/blood.v120.21.1569.1569 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1569-1569

Author(s):

Daxing Zhu ◽

Offiong F Ikpatt ◽

Sander R Dubovy ◽

Yasodha Natkunam ◽

Jennifer R Chapman-Fredricks ◽

...

Keyword(s):

B Cell ◽

Copy Number ◽

Chromosomal Alterations ◽

Dual Color ◽

Pathway Activation ◽

Myd88 L265p Mutation ◽

Igh Rearrangement ◽

Myd88 L265p ◽

A20 Gene ◽

Antigen Selection

Abstract Abstract 1569 Ocular adnexal mucosa associated lymphoid tissue lymphomas (OAMALTL) are the most common lymphomas of the eye. The etiology and pathogenesis of ocular adnexa MALT lymphomas (OAMALTL) are still unknown and the association with Chlamydophila psittaci (C. psittaci) has been shown in only some geographic regions. Only few small studies specifically examined for the presence of t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH, t(14;18)(q32;q21)/IGH-MALT1, t(3;14)(p13;q32)/FOXP1-IGH translocations or for TNFAIP3 (A20) mutations/deletions, which may contribute to the activation of canonical nuclear factor (NF)-kB pathway in OAMALTL. Herein we sought to comprehensively examine the frequency of these translocations as well as CARD11 and MYD88 (L265P) mutations, in addition to A20 mutations /deletions in a large cohort of C. psittaci negative OAMALTL. A total of 47 OAMALTL originating in the orbit (22), conjunctiva (19) and lacrimal gland (6) were used for analysis. Dual color fusion probes for t(14;18)(q32;q21) IGH-MALT1, t(11;18)(q21;q21) BIRC3-MALT1 and dual color break apart probes for MALT1, BCL6, and CEP18 (chromosome 18 centromere) were used for FISH analysis in all the analyzed tumors. Dual color break apart probe for IGH was used for selected tumors. Extracted DNA was used for PCR amplification and sequencing of the coiled-coil domain of CARD11, exon 5 of MYD88, in which the L265P mutation was previously reported in diffuse large B-cell and MALT lymphomas, and all the coding exons of the A20 gene. A20 gene copy number variation was analyzed by TaqMan Copy Number Assay (Applied Biosystems). DNA extracted from peripheral blood lymphocytes of 3 healthy volunteers and OCI-LY8 and Jeko-1 cell lines served as calibrator and positive controls for A20 deletion. CARD11 mutations were not found in all the analyzed tumors. The MYD88 L265P mutation was detected in 3 (6.4%) tumors. A total of 9 A20 mutations were identified in 7 (14.9%) tumors. One tumor harbored 3 distinct mutations (F149C; 1bp deletion in exon 3 and 2bp deletion in exon 5). Among the 9 detected A20 mutations, the majority (89%) would produce truncated proteins due to out-frame insertion/deletion (7), while one of these deletions was located in a known splicing site. Only 2 missense mutations were observed, including one in a tumor in which 2 concomitant deletions were also present (described above). A20 heterozygous deletions were detected in 7 (14.9%) tumors. There was no association between A20 mutations and heterozygous deletion in any of the analyzed tumors. None of the tumors harbored a concomitant A20 mutation/deletion and MYD88 L265P mutation. A total of 5 tumors harbored chromosomal alterations: additional copy of BCL6, most probably due to trisomy 3, in 2 tumors, an additional copy of IGH in 1, extra copies of both IGH and MALT1 in 1, and extra copies of IGH, MALT1, BIRC3 together with IGH rearrangement to unidentified partner in 1. t(14;18)(q32;q21) IGH-MALT1 and t(11;18)(q21;q21) BIRC3-MALT1 were not detected in any of the analyzed tumors. A20 mutations were detected in a tumor with extra signals of both IGH and MALT1 genes as well as in one of the tumors with an additional copy of BCL6. The tumor with complex chromosomal aberrations including the IGH rearrangement to an unidentified partner also harbored A20 deletion. 26 of the analyzed tumors previously were shown to exhibit evidence of antigen selection based on the analysis of IGHV mutation pattern (PLoS One. 2011;6(12):e29114). There was no association between antigen selection and A20 mutations/deletions, MYD88 (L265P) mutation and chromosomal alterations. Overall, our data suggest that translocations characteristic for MALT lymphomas are rarely observed in OAMALTL. The MYD88 (L265P) mutation is also uncommon, while most of the A20 mutations/deletions affect only one allele and thus most probably do not lead to NF-kB activation. This raises a question on what are the mechanisms for canonical NF-kB signaling pathway activation in OAMALTL and if it is indeed activated in these tumors. It is possible that NF-kB signaling pathway activation maybe due to B cell receptor signaling, as may be reflected by association with presence of antigen selection that is observed in major fraction of these tumors. Immunohistochemical studies addressing these questions are underway and will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

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The Clinical Impact of Minimal Bone Marrow Involvement on the Outcome of Patients with Follicular Lymphoma

Blood ◽

10.1182/blood.v128.22.2966.2966 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2966-2966

Author(s):

Daisuke Kato ◽

Satoshi Yoshioka ◽

Tomohiro Yabushita ◽

Yoshimitsu Shimomura ◽

Yuichiro Ono ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

Prognostic Index ◽

Morphological Evidence ◽

Stage Disease ◽

Igh Rearrangement ◽

The Impact ◽

Index Table

Abstract Introduction: Follicular lymphoma (FL) is the second most common type of non-Hodgkin cell lymphoma, and usually manifests as a disseminated disease. Bone marrow (BM) involvement, which occurs in 40-70% of cases, is often seen in follicular lymphoma and thought to be associated with less favorable prognosis. Diagnosis of BM involvement has traditionally been based on morphological findings, and BM involvement has been determined using histology alone in most clinical trials. Immunocytologic or molecular studies, such as flow cytometry (FCM) and polymerase chain reaction (PCR), have become more readily available, and their usage has clearly documented minimal BM involvement reproducibly. In this study, we evaluated the impact of BM involvement detected by FCM and PCR on the outcome of patients treated for FL. Methods: Patients who were diagnosed with biopsy-proven FL between 2004 and 2015 at our institution were included in the study. All patients had received a staging bone marrow examination before treatment with immunotherapy-based regimen. Immunocytologic [FCM] and/or molecular [PCR] studies were always performed if the patients did not have morphological BM involvement. We used 4- or 6- color FCM, and performed PCR analysis of Bcl-2/IgH rearrangement and/or IgH rearrangement detected by modified BioMed-2 protocol. A total of 90 patients were included, and the median follow-up duration was 36 months (range, 6|122 months). The BM status was classified using into 3 categories: morphological, minimal, and negative BM involvement. Minimal BM involvement was defined as BM involvement detected by FCM or PCR without morphological evidence. Morphological and minimal BM involvements were detected in 37 (41%) and 38 (42%) patients, respectively. The primary outcome measure was progression-free survival (PFS). PFS curves were plotted using the Kaplan-Meier method and compared by the log-rank test. Multivariate analyses were performed using a Cox linear regression model. There were significant differences in gender, LDH levels, stage, nodal sites, and FL International Prognostic Index (FLIPI) between patients with and without morphological BM involvement (Table1). Results: The 3-year PFS rate for patients with negative BM involvement was significantly better than that for patients with minimal or morphological BM involvement (84.8% vs. 40.3% vs. 60.5%; p= 0.043) (Figure 1). There was no statistical difference in 3-year PFS between patients with morphological BM involvement and those with minimal BM involvement. The difference of 3-year PFS rate between patients with minimal BM involvement and those with negative BM involvement was significant for patients with FLIPI low-intermediate risk (88.9% vs. 51.5%; p= 0.032) and those with advanced stage disease (90.0% vs. 33.6%; p= 0.027), but there were no significant differences in patients deemed FLIPI high risk and those with limited stage disease. Multivariate analysis revealed that BM involvement, including morphological and minimal involvement, was a significant poor prognostic factor (hazard ratio 4.885 [95% confidence interval 1.16-20.56], p = 0.0305). Conclusion: At the start of treatment, bone marrow involvement was seen in most FL patients. Patients without any BM involvement had an excellent prognosis. Patients with minimal BM involvement had an equally poor prognosis as those with morphologic BM involvement. Table 1 FLIPI: Follicular Lymphoma International Prognostic Index Table 1. FLIPI: Follicular Lymphoma International Prognostic Index Table 2 BM state positive: including morphological and minimal bone marrow involvement. Table 2. BM state positive: including morphological and minimal bone marrow involvement. Figure Figure. Disclosures Ishikawa: Mundipharma KK: Research Funding.

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