Prognostic Significance of Magnetic Resonance Imaging (MRI) of Bone Marrow (BM) in Patients with Multiple Myeloma (MM) Undergoing Treatment with High-Dose Melphalan (HDM) and Autologous Stem Cell Transplantation (ASCT).

Abstract Purpose: We have previously reported that diffuse pattern of bone marrow involvement as determined by MRI imaging of the spine, in newly diagnosed patients with MM is associated with features of advanced disease and with shorter survival compared to patients with normal, focal or variegated pattern of BM involvment. Purpose of the study was to determine the prognostic value of spinal bone MRI in the outcome of MM patients undergoing treatment with HDM and ASCT. Materials and methods: Between October 1995 and June 2006, 63 MM patients for whom a MRI of the spine before first line therapy was available, received treatment with HDM (200mg/m2 iv) and ASCT, in our Department. Four patterns of BM involvement in MRI were identified: normal pattern which required no evidence of abnormal signal, focal pattern, which consists of localized areas of abnormal marrow (on T1-weighted images, focal lesions are darker than yellow marrow and slightly darker or isointense to red marrow; on T2-weighted images they are brighter than both red and yellow marrow), diffuse pattern of abnormal marrow, where the normal bone marrow is completely replaced by the abnormal process and the intervertebral discs appear brighter or are isointense to the diseased marrow, and variegated pattern, which consists of innumerable small foci of disease on a background of intact marrow. MRI pattern of BM involvement and multiple clinical and laboratory parameters were evaluated for their possible correlation with progression free survival (PFS) after HDM. Results: Patients’ median age was 55years (range: 23 to 74 years), 60% of patients had ISS 2 or 3 before initial treatment, 54% of patients were transplanted during remission and 46% of patients had active myeloma at the time of HDM (primary refractory: 34%, resistant relapse: 12%). Nine patients (14%) had a normal MRI pattern, 33 (53%) had focal, 4 (6%) variegated and 17 (27%) diffuse MRI pattern of BM involvement. The median PFS for all patients was 20 months. Significant adverse prognostic factors for PFS included elevated creatinine and LDH serum levels, and ISS stage 3 at diagnosis. Furthermore the pattern of BM involvement by MRI correlated strongly with PFS: median PFS of 72 months for normal pattern, 20 months for focal pattern, 16 months for variegated and 9 months for diffuse pattern (p=0.016). Patients with both ISS stage 3 and diffuse MRI pattern had a median PFS of only 6 months. Conclusion: MRI of the spine before treatment provides prognostic information for the outcome of MM patients with myeloma after HDM and ASCT. Diffuse marrow replacement on MRI of the spine identifies patients with advanced MM who have a poor prognosis even after intensive therapy. Such patients are candidates for innovative treatments.

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Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.6.1336 ◽

1995 ◽

Vol 13 (6) ◽

pp. 1336-1342 ◽

Cited By ~ 44

Author(s):

Y Yan ◽

W C Chan ◽

D D Weisenburger ◽

J R Anderson ◽

M A Bast ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

B Cell Lymphoma ◽

High Dose Chemotherapy ◽

High Dose ◽

Term Survival

PURPOSE We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS Patients with BM involvement that consisted of > or = 50% large cells or BM involvement of > or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of < or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved > or = 70% of the marrow or contained > or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI < or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.

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Clinical and Prognostic Relevance of Magnetic Resonance Imaging of the Spine in Newly Diagnosed Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.4885.4885 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4885-4885

Author(s):

Patrizia Tosi ◽

Alessandro Petrucci ◽

Lucia Pantani ◽

Elena Zamagni ◽

Paola Tacchetti ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Bone Marrow Involvement ◽

Progression Free Survival ◽

High Dose ◽

Newly Diagnosed ◽

Resonance Imaging ◽

Focal Lesions ◽

Free Survival ◽

Focal Pattern

Abstract Abstract 4885 Magnetic resonance imaging (MRI) of the spine has demonstrated to be a useful tool for a correct staging of multiple myeloma (MM), as it is more sensitive than plain x-rays in detecting vertebral lesions. Furthermore, both pattern of bone marrow involvement (focal, diffuse or normal), and number of focal lesions can be detected, and this could contribute to better define the prognosis and the outcome of newly diagnosed patients. In the present study we prospectively evaluated the clinical and prognostic role of spinal MRI in 152 newly diagnosed MM patients (89M, 63F, median age = 56yrs) that subsequently received high-dose chemotherapy and autologous stem cell transplantion, either single (n=43) or double (n=109). Pattern of marrow involvement was normal in 11% of the cases, diffuse in 20% and focal in 69%, with 34% of the patients showing > 7 focal lesions. Patients with a diffuse pattern or a focal pattern with > 7 lesions showed a significantly higher bone marrow plasma cell infiltration (p=0.04) and beta2 microglobulin values (p= 0.04) as compared to patients with a focal pattern with < 7 lesions. Response rate to the assigned treatment program was similar in the three groups of patients, with > VGPR obtained in 63% of the patients with a diffuse pattern, and in 70% of those with a focal pattern. Median progression-free survival (PFS) was significantly longer in patients with < 7 focal lesions as compared to those with >7 lesions or a diffuse pattern (55 vs 46 months p=0.05). Normalization of MRI was more frequently obtained in patients with < 7 lesions (67% vs 38% in patients with > 7 lesions, p=0.005); patients achieving a normal MRI pattern showed a significantly longer PFS (67 months) as compared to patients failing to achieve a negative MRI at the end of treatment (p=0.0000). According to our data, MRI confirms its prognostic role in newly diagnosed MM receiving high-dose therapy and autologous stem-cell transplantation; a diffuse pattern of bone marrow involvement or a focal pattern with > 7 lesions are predictive of a more aggressive outcome of the disease; furthermore normalization of MRI pattern after therapy is predictive of a longer progression-free survival Disclosures No relevant conflicts of interest to declare.

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Clinical Significance of Bone Marrow Imaging of Appendicular Skeletons By Low-Dose Multi-Detector Computed Tomography in Patients with Bone Marrow Failure Syndrome

Blood ◽

10.1182/blood.v126.23.1690.1690 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1690-1690

Author(s):

Manabu Fujisawa ◽

Yasuhito Suehara ◽

Kota Fukumoto ◽

Yoshiaki Usui ◽

Kentaro Narita ◽

...

Keyword(s):

Bone Marrow ◽

Low Dose ◽

Bone Marrow Failure ◽

High Density ◽

Appendicular Skeleton ◽

Bone Marrow Failure Syndrome ◽

Red Marrow ◽

Yellow Marrow ◽

Focal Pattern ◽

The Relationship

Abstract Background: Aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndrome (MDS) are the heterogeneous group of bone marrow failure syndrome (BMFs). AS they often show profound hypocellular marrow, the diagnosis is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the age of early 20s. Although abnormal distribution of red marrow in appendicular skeleton were previously reported in small series of patients with MDS, leukemia and lymphoma by MRI, no further study has published so far. Here, we examined distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in BMFs patients, and analyzed the relationship between the abnormal medullary pattern in AS and laboratory variables. The relationship between the MDCT pattern and subsequent development of leukemic transformation on survivals was analyzed in patients with BMFs. Patients: We retrospectively reviewed the medical records of 138 untreated patients (AA n=36, PNH n=5, and MDS n=97) with BMFs diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. Follow-up MDCTs were evaluated in 28 MDS patients when they were diagnosed as overt AML (MDS/tAML). Retrospective review of clinical and laboratory features including complete blood count, % of bone marrow blast, chromosomal analysis, and International Prognostic Scoring System (IPSS) at diagnosis was performed. WHO classification of patients with MDS was as follows: RCUD (n=21), RARS (n=2), RCMD (n=26), RAEB (n=43), and, MDS unclassified (MDS-U) (n=5). Leukemia-free survival (LFS) and overall survival (OS) were analyzed in 73 patients with MDS who were ≥65 years of age and ineligible for allogeneic stem cell transplantation (allo SCT) by the Kaplan-Meier. CT image acquisition and Image analysis: Non-enhanced CT examinations were performed from the skull to the knees by MDCT scanner (Aquilion 64, Tohshiba, Tokyo, Japan). Bony canal of humeral and femoral bone were visualized by coronal and sagittal axis image reconstruction. Medullary CT density of humerus and femurs were measured and the results were expressed as Hounsfield unit (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by low density CT value between -30 to -100 HU. The value above -30 HU observed in long bony canals was considered as high density. Medullary pattern of AS were categorized as follows: (1) fatty pattern; showing a low signal density marrow (2) focal pattern; showing abnormally focal high density lesions (3) diffuse pattern; showing uniformly high density marrow. Results: All 36 patients with AA showed a fatty (n=13, 36.1%) or focal (n=23, 63.9%) pattern in medullary AS on MDCT, and none of them showed diffuse pattern. Five patients with PNH showed as follows: fatty/focal/diffuse, 1/3/1. Ninety-seven patients with MDS showed as follows: fatty/focal/diffuse, 24/46/27. Patients with MDS who showed diffuse pattern had a significantly low hemoglobin concentration compared to those with fatty or focal pattern (p=0.03). Among the patients with MDS, most of the patients with RCUD (n=21), RARS (n=2), RCMD (n=26), MDS-U (n=5) showed the fatty or focal pattern (fatty or focal/diffuse pattern; RCUD (18/3), RARS (2/0), RCMD (21/5), MDS-U (5/0)), but approximately half (46%) of patients with RAEB showed diffuse pattern (fatty/focal/diffuse pattern; 7/17/19). In addition, patients with transformed to MDS/tAML showed either focal (n=10, 35.7%) or diffuse (n=18, 64.3%) pattern and none of them showed fatty pattern. In 73 patients with MDS who were ≥65 years of age and ineligible for allo SCT, the group with focal or diffuse pattern had significantly shorter LFS and OS compared to the group with fatty pattern (p=0.01, p=0.05, respectively). Patients with focal pattern in AS showed longer LFS than those with diffuse pattern (p=0.05), but difference was not statistically significant in OS (p=0.22). Conclusions: This study showed that MDCT imaging of the appendicular skeletons provided important information for the diagnosis and prognosis of patients with BM. In patients with MDS, focal or diffuse pattern on MDCT showed negative prognostic impact on LFS and OS, and these patterns appeared to reflect the status of disease. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

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The Evaluation of Clinical and Molecular Response to High-Dose Chemotherapy Protocol NHL BFM-90 in Adults with Anaplastic Large Cell ALK-Positive Lymphoma

Blood ◽

10.1182/blood.v118.21.1622.1622 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1622-1622

Author(s):

Liliya Gorenkova ◽

Sergey K Kravchenko ◽

Yulia Vinogradova ◽

Ekaterina Ilyushkina ◽

Andrey Misurin ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Bone Marrow Involvement ◽

Prognostic Significance ◽

Large Cell ◽

Adult Patients ◽

High Dose ◽

Molecular Response ◽

Chimeric Transcript ◽

Alk Positive

Abstract Abstract 1622 Background: Anaplastic large cell ALK-positive lymphoma (ALCL) is a rare disease in adult population and represents 3% of all lymphomas. It‘s characterized by the expression of surface antigen CD30, translocations involving gene 2p23, and leading to the formation of chimeric transcripts with ALK protein. The optimal treatment and predictive factors are not well defined in adult patients. The most commonly used regimens are CHOP-like programs, which have shown 30–65% 5-year overall survival (without stage stratification). The application of the protocol NHL BFM-90 in pediatric practice in Germany has improved the results of the treatment and allowed to achieve 80–100% overall survival rate (Reiter A. 2001). So we decided to initiate a pilot study aiming to intensity treatment approach in adults with ALCL. Goal: to evaluate the efficacy of chemotherapy intensification with NHL BFM-90 protocol and to investigate the prognostic significance of molecular markers in adults with ALCL. Materials and methods: From 2000 to 2011 year 20 patients with a median age of 26 years (17–65 years old) were enrolled in the study (14 men and 6 women). We have found generalized lymphadenopathy in all patients, high frequency of extranodal sites involvement (40%), bone marrow involvement proved by morphology in 2 patients (10%). II stage was diagnosed in 5 patients (25%), III-IV stage - in 15 patients (75%). We used program NHL BFM-90, branches K2 or K3 (the dose of methotrexate was different in two branches: 1g/m2 in branch K2, 5g/m2 in branch K3). The choice of the branch depended on the stage and clinical prognostic factors (III and IV stage, mediastinum, skin, lung, testis, central nervous system and bone marrow involvement). ALK gene rearrangement was determined by fluorescent in situ hybridization in all patients. Blood and bone marrow samples have been examined for the quantity of chimeric transcript by real time PCR before the treatment and after the end of protocol NHL BFM-90 (median treatment duration 4 months). The informed consent was obtained from all patients. Results: 19 from 20 patients (95%) have achieved complete remission (usually after 4 courses of chemotherapy). One patient died of infectious complications during the first course of chemotherapy. Early relapse was occurred in two patients (11%). 5-year overall survival is 90%. Blood and bone marrow samples before and after treatment were available in 12 from 20 patients. We were able to determine the chimeric transcript in 4 patients (3 cases NPM-ALK, 1 case ATIC-ALK) before treatment including those without morphological bone marrow involvement. After chemotherapy only one patient had chimeric transcript in blood (1,12% copies of gene NPM-ALK/ABL expressed in percents). He has relapsed one year after the end of the treatment. Other patients with the absence of the chimeric transcript are still in remission. Conclusions: protocol NHL BFM-90 has shown the high efficacy in adult patients with ALCL compared with currently used chemotherapy regimens. The presence of minimal residual disease after the treatment is probably a new adverse prognostic factor. Disclosures: No relevant conflicts of interest to declare.

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Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma

Blood ◽

10.1182/blood.v86.8.3257.bloodjournal8683257 ◽

1995 ◽

Vol 86 (8) ◽

pp. 3257-3262 ◽

Cited By ~ 1

Author(s):

Y Bastion ◽

P Brice ◽

C Haioun ◽

A Sonet ◽

G Salles ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Peripheral Blood ◽

Poor Prognosis ◽

Intensive Therapy ◽

Bone Marrow Involvement ◽

Autologous Bone Marrow Transplantation ◽

Conditioning Regimen ◽

High Dose ◽

Patients With Poor Prognosis

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

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Bone Marrow Imaging of Appendicular Skeleton by Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Hypoplastic MDS.

Blood ◽

10.1182/blood.v120.21.2817.2817 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2817-2817

Author(s):

Tomotaka Ugai ◽

Hiroki Sugihara ◽

Yuki Nishida ◽

Masayuki Yamakura ◽

Masami Takeuchi ◽

...

Keyword(s):

Bone Marrow ◽

Who Classification ◽

Low Dose ◽

High Density ◽

Whole Body ◽

Appendicular Skeleton ◽

Bone Marrow Blast ◽

Red Marrow ◽

Yellow Marrow ◽

Focal Pattern

Abstract Abstract 2817 Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are the heterogeneous group of bone marrow failure disorders. AS both shows profound hypocellular marrow without minimal morphologic atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion is occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the age of early 20s. Although abnormal distribution of red marrow in appendicular skeleton has previously reported in small series of patients with MDS, leukemia and lymphoma by MRI, no further study has published so far. Here, we examined distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationship between the abnormal medullary pattern in AS with laboratory variables, subsequent development of leukemic transformation and survivals MDS patients. Patients: We performed a low-dose MDCT of humerus and femurs in 64 untreated adult patients with AA (N=15) and MDS (N=49). Retrospective review of clinical and laboratory features including complete blood count, % of bone marrow blast, chromosomal analysis, and International Prognostic Scoring System (IPSS) was performed. WHO classification of MDS patients was as follows: RA (N=17), RARS (N=2), RCMD (N=9), RAEB (N=19) and MDS unclassified (N=2). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 49 MDS patients by the Kaplan-Meier and differences between curves were calculated by two-sided log-rank test. Multivariate analysis was Used to assess the effects of prognostic factors - hemoglobin, platelet, bone marrow blast, cytogenetic abnormalities, IPSS score, WHO classification, and MDCT patterns. CT image acquisition and Image analysis: Non-enhanced CT examinations were performed from the base of skull down to the knee joint by MS-CT scanner (AQUILION 64, Tohshiba, Tokyo, Japan). Bony canal of humeral and femoral bone were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole body MD-CT was 10.1 mSv. (ICRP 26). The dose was comparable to whole body CT (2.4 mSv.). Medullary CT density of humerus and femurs were measured and the results were expressed as Hounsfield unit (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by low density CT value between −30 to −100 HU. The value above −30 HU observed in long bony canals was considered as high density lesions. Medullary pattern of appendicular skeletons were categorized as follows: (1) fatty; showing a low signal density marrow (2) focal; showing abnormally focal high density lesions: (3) diffuse; showing uniformly high density marrow. Results: All 15 patients with AA showed a fatty (N=10, 66%) or focal (N=5, 33%) pattern in medullary AS on MDCT and none of them showed diffuse pattern. Conversion from fatty to focal marrow was observed in 9 of 15 AA patients after successful immunosuppressive treatment. Among the 49 patients with MDS, 15 (31%) had fatty pattern, 21 (43%) had focal pattern, and 13 (27%) had diffuse pattern. Patients with diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration (p<0.01) and shorter OS (p<0.01) compared to those with fatty or focal medullary pattern. The characteristics of the patients with diffuse pattern did not differ significantly in terms of sex, age, WBC count or karyotype from those of the patients with fatty or focal pattern. Among 13 MDS patients with diffuse pattern, 6 developed AML during their follow-up periods (median, 17 months; range, 2 to 38 months). LFS and OS of 13 patients with diffuse patterns were significantly shorter than that of the 36 patients with fatty and focal patterns (74% vs 19% at 3 years; p<0.01 and 79% vs 40% at 3 years; p<0.01, respectively). On multivariable analysis, diffuse pattern on MDCT was emerged as independently negative prognostic impact on LFS and OS in patients with MDS. Conclusions: This study showed that MDCT imaging of the appendicular skeletons provided important information for the diagnosis and prognosis of patients with MDS and AA. Disclosures: No relevant conflicts of interest to declare.

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Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma

Blood ◽

10.1182/blood.v86.8.3257.3257 ◽

1995 ◽

Vol 86 (8) ◽

pp. 3257-3262 ◽

Cited By ~ 127

Author(s):

Y Bastion ◽

P Brice ◽

C Haioun ◽

A Sonet ◽

G Salles ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Peripheral Blood ◽

Poor Prognosis ◽

Intensive Therapy ◽

Bone Marrow Involvement ◽

Autologous Bone Marrow Transplantation ◽

Conditioning Regimen ◽

High Dose ◽

Patients With Poor Prognosis

Abstract Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

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Myeloid sarcoma: experience from a hematology care centre of Eastern India

10.25259/jhas_9_2021 ◽

2021 ◽

Vol 1 ◽

pp. 33-37

Author(s):

Avriti Baveja ◽

Prakas Kumar Mandal ◽

Malini Garg ◽

Prakash Singh Shekhawat ◽

Sumit Mitra ◽

...

Keyword(s):

Bone Marrow ◽

Intensive Therapy ◽

Bone Marrow Involvement ◽

Young Patients ◽

Case Series ◽

Clinicopathological Characteristics ◽

Myeloid Sarcoma ◽

Cytogenetic Abnormality ◽

High Dose

Objectives: To describe the case series of patients with myeloid sarcoma with their clinicopathological characteristics, cytogenetics, molecular markers, prognosis, and outcome. Material and Methods: Retrospective retrieval of data of myeloid sarcoma cases in acute myeloid leukemia was done from the electronic health records of our hospital and this case series includes the data of three years starting from January 2018 and the follow-up information was assimilated until December 2020. Results: We present twelve patients in this case series with myeloid sarcoma and all these patients had bone marrow involvement at presentation. Most of the cases were less than 20 years of age and orbit (66.7%) was the commonest site of presentation in this series. Aberrant CD 19 expression on immunophenotyping was a common associate (66.9%) and t(8;21) was the commonest cytogenetic abnormality reported in our case series. Despite of high dose intensive therapy with daunorubicin and cytarabine followed by high-dose cytarabine (HiDAC) consolidation, patients had a median relapse-free survival and median overall survival of 160 days and 299.5 days respectively. Local radiotherapy for consolidation in two of our patients had no additional benefit. Conclusion: Myeloid sarcoma is extramedullary collection of myeloid blasts with or without bone marrow involvement. They were commonly seen in young patients and t(8;21) being a common cytogenetic abnormality associated with it. The treatment outcome of patients with myeloid sarcoma seems dismal and systemic therapy remains the modality of choice.

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Clinical and Prognostic Significance of Bone Marrow Imaging of Appendicular Skeletons By Low-Dose Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Myelodysplastic Syndorme

Blood ◽

10.1182/blood.v124.21.5602.5602 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5602-5602

Author(s):

Manabu Fujisawa ◽

Tomotaka Ugai ◽

Yasuhito Suehara ◽

Keisuke Seike ◽

Kota Fukumoto ◽

...

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Low Dose ◽

High Density ◽

Whole Body ◽

Appendicular Skeleton ◽

Diffuse Infiltration ◽

Red Marrow ◽

Yellow Marrow ◽

Focal Pattern

Abstract Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) comprise a heterogeneous group of bone marrow failure disorders. As both show profound hypocellular marrow with minimal morphological atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the early 20s. Although an abnormal distribution of red marrow in AS has previously been reported in small numbers of patients with MDS, along with leukemia and lymphoma by MRI, there have been no further reports to date. Here, we examined the distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationships between the abnormal medullary pattern in AS and laboratory variables, subsequent development of leukemic transformation, and survival in MDS patients. Patients: We performed low-dose MDCT of the humerus and femur in 103 untreated adult patients with AA (n = 32) and MDS (n = 71). We retrospectively reviewed the medical records of patients with AA and MDS diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. A retrospective review of clinical and laboratory features, including complete blood count, % bone marrow blasts, chromosomal analysis, and International Prognostic Scoring System (IPSS), was performed. WHO classification of MDS patients was as follows: RA (n = 22), RARS (n = 2), RCMD (n = 17), RAEB 1 (n = 18), RAEB 2 (n = 11), and MDS unclassified (n = 1). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 71 MDS patients by the Kaplan–Meier method and differences between curves were calculated by two-sided log-rank test. CT image acquisition and image analysis: Non-enhanced CT examinations were performed from the base of the skull down to the knee joint with an MS-CT scanner (AQUILION 64; Toshiba, Tokyo, Japan). The bony canals of the humeral and femoral bones were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole-body MD-CT was 10.1 mSv (ICRP 26). The dose was comparable to whole-body CT (2.4 mSv). Medullary CT density of the humerus and femur were measured and the results are expressed in Hounsfield units (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by a low-density CT value between –30 and –100 HU. A value above –30 HU observed in long bony canals was considered to indicate a high-density lesion. The medullary pattern of the appendicular skeleton was categorized as follows: (1) fatty, showing a low signal density marrow; (2) focal, showing abnormally focal high-density lesions; (3) diffuse, showing uniformly high-density marrow. Results: All 15 patients with AA showed a fatty (n = 12, 37.5%) or focal (n = 20, 62.5%) pattern in medullary AS on MDCT, and none showed a diffuse pattern. Among the 71 patients with MDS, 22 (30.9%) had a fatty pattern, 32 (45.1%) had a focal pattern, and 17 (23.9%) had a diffuse pattern. Seventeen patients with diffuse infiltration pattern on MDCT had significantly shorter LFS (P < 0.01, P = 0.02) compared to 23 patients with fatty pattern and 32 patients with focal medullary pattern (median LFS: 18 months vs. not reached vs. not reached, respectively). Seventeen patients with a diffuse infiltration pattern on MDCT had significantly shorter OS (P = 0.04) compared to 23 patients with a fatty pattern, but the difference was no significant compared to 32 with a focal medullary pattern (P = 0.15) (median OS: 22 months vs. not reached vs. not reached, respectively). The characteristics of the patients with diffuse pattern did not differ significantly in terms of sex, age, WBC count, platelet count, karyotype, WT1, or IPSS classification from those of patients with a fatty or focal pattern, but patients with a diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration compared to those with a fatty or focal medullary pattern (P = 0.03). Conclusions: This study showed that MDCT imaging of the appendicular skeleton provided important information for the diagnosis and prognosis of patients with MDS and AA. In patients with MDS, a diffuse pattern on MDCT emerged as an independent negative prognostic indicator on LFS and OS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8029 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8029-8029

Author(s):

Binod Dhakal ◽

Shruti Sharma ◽

Svetlana Shchegrova ◽

Minu Maninder ◽

Meenakshi Malhotra ◽

...

Keyword(s):

Bone Marrow ◽

Residual Disease ◽

Prognostic Significance ◽

Unmet Need ◽

Progression Free Survival ◽

Multiparameter Flow Cytometry ◽

High Dose ◽

Blood Samples ◽

Ctdna Analysis

8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here we attempt to evaluate MRD using ctDNA in AHCT recipients with MM. Methods: In this retrospective, single-center study, we analyzed ctDNA MRD in blood samples collected from 28 patients with MM after upfront AHCT. A total of 80 plasma timepoints were available pre and post AHCT with a median follow-up of 92.4 months. Multiparameter flow cytometry (MFC) at 10-4 level was used to assess the MRD from the BM biopsy. Individual bone marrow aspirates or FFPE slides from the time of MM diagnosis and matched normal blood were whole-exome sequenced, and somatic mutations were identified. MRD assessment at 3 months post-AHCT was performed by ctDNA analysis using a personalized, tumor-informed (SignateraTM, bespoke mPCR NGS assay). The prognostic value of ctDNA was evaluated by correlating MRD status with clinical outcomes. Results: Table provides the baseline disease characteristics. Median age was 67 [41-75] years and 16 [57.1%] were males. ctDNA was detectable in 70.8% (17/24) of pre-AHCT, 53.6% (15/28) of ̃3 months post-AHCT, and 39.2% (11/28) of patients during the surveillance phase post-AHCT. Of the 15 ctDNA MRD positive patients, 93.3% (n=14) experienced relapse on follow-up (hazard ratio: 5.64; 95% CI: 1.8-17; p=0.0003). Patients negative for ctDNA at 3 months post-AHCT had significantly superior progression-free survival (PFS) compared to positive (median PFS, 84 months vs. 31 months; p=0.003) The positive predictive value (PPV) for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, and significantly higher than marrow MFC of 68.4%. Conclusions: Our study shows the feasibility that a tumor-informed assay on archival blood samples is predictive of relapse post-AHCT. Future prospective studies with real-time marrow NGS and ctDNA samples are needed to define the role of ctDNA in MM and its prognostic significance.[Table: see text]

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