Semen quality in non-Hodgkin lymphoma survivors: a monocentric retrospective study

Abstract STUDY QUESTION How is semen quality affected by treatment in survivors of non-Hodgkin lymphoma (NHL)? SUMMARY ANSWER Before cancer treatment, most NHL subjects were normozoospermic and, while standard first-line treatments seemed compatible with post-treatment recovery after 18 months, salvage therapy followed by haematopoietic stem cell transplant caused permanent damage to spermatogenesis in many cases, with 66% azoospermic subjects in the long term. WHAT IS KNOWN ALREADY Testicular function has been widely investigated in relation to the most common malignancies in men of reproductive age, such as testicular cancer and Hodgkin lymphoma, but NHL has been somewhat under-investigated. The available reports generally show a post-treatment worsening of semen parameters in NHL survivors, but they involved small caseloads or a subgroup of broader caseloads, and their results are not comparable. STUDY DESIGN, SIZE, DURATION We conducted a retrospective analysis of 222 subjects who attended our University Hospital Sperm Bank between 2002 and 2017 for sperm cryopreservation after a diagnosis of NHL. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included 222 patients with NHL who underwent sperm cryopreservation before any antineoplastic treatment. Subjects with any comorbidity and/or other conditions interfering with sperm parameters were excluded. All patients underwent a careful medical history and physical examination at the time of sperm cryopreservation (T0) and had at least one follow-up visit at 6 (T6), 12 (T12), 18 (T18) and/or 24 months (T24) or more than 24 months (T > 24), with a median follow-up of 47.5 months (range 28–140 months). Fertility information was collected through the administration of a questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE Pre-treatment, more than 80% of NHL patients were normozoospermic and in 15.9% of cases had already fathered a child. Aggressive lymphomas were associated with worse baseline semen volume and total sperm number compared to indolent subtypes (P < 0.05). Post-treatment analyses showed that standard first-line treatments alone had a more favourable outcome than intensified regimens for semen parameters, with total sperm number returning to near-baseline values at 18 months (T0: 195.0 ± 189.8 versus T18: 113.4 ± 103.1, P = 0.278), and a 7.7% prevalence of azoospermia at 2 years. In this subgroup receiving standard first-line treatments, radiotherapy of the pelvis versus other ‘high’ sites (mediastinum, latero-cervical and axillary lymph nodes, etc.) was associated with an increased risk of developing post-treatment azoospermia (odds ratio 4.29, 95% CI 1.81–10.14; P = 0.001). Two-thirds of subjects who had relapsed or had disease progression after first-line treatment and then underwent salvage treatment ± haematopoietic stem cell transplant became azoospermic. Fertility data were available for 176 patients: 15.9% already had at least one child prior to the NHL diagnosis and 12.5% (22 patients) desired children after treatment. Fourteen patients achieved fatherhood: 12 through natural conception and two following ART. LIMITATIONS, REASONS FOR CAUTION The main limitations of the study are the lack of data on blood hormones for evaluation of testicular function as a whole and the non-compliance of several patients in attending follow-up visits at all time points, resulting in a reduced sample size for the treatment subgroup analyses. Furthermore, despite a good fertility questionnaire response rate (>80%), the low number of NHL survivors actively seeking fatherhood limits the generalization of results. WIDER IMPLICATIONS OF THE FINDINGS The increased survival of NHL patients of reproductive age makes it essential to focus on the testicular toxicity of the treatment. Sperm cryopreservation must be suggested before any treatment. Two years after first-line treatments, sperm number showed signs of recovery: this finding is of the utmost importance for oncofertility counselling, as it indicates that only a standard first-line chemotherapy in many patients may be compatible with at least a partial spermatogenesis recovery in the long term. Nonetheless, it is expected that up to 30% of subjects will require treatment intensification, which could result in permanent testicular damage; in such cases the use of banked semen might represent the patient’s best chance for future fertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a grant from the Italian Ministry of Education and Research (MIUR-PRIN 2015-2015XSNA83-002) and the ‘Sapienza’ University of Rome, Faculty of Medicine. The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Download Full-text

Long Term Molecular Remissions after Autologous Haematopoietic Stem Cell Transplant in Follicular Lymphoma.

Blood ◽

10.1182/blood.v112.11.2185.2185 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2185-2185

Author(s):

Séverine Lissandre ◽

Patrick Vourch ◽

Isabelle Desbois ◽

Lotfi Benboubker ◽

Caroline Dartigeas ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

First Line ◽

Molecular Remission ◽

Remission Duration

Abstract Background and aim of the study: Autologous stem cell transplant (ASCT) has been shown to be an effective treatment for first-line and relapsed follicular lymphomas (FL). But no long term molecular remission was described. The aim of this retrospective study was to determine the clinical and molecular outcome of patients with FL who received ASCT during a 12-year period. Method: All patients who underwent ASCT for first-line or relapsed FL between January 1992 and December 2004 were included. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method and cumulative incidence of nonrelapse mortality (NRM), with relapse as a competing event, by Fine and Gray method. Patient characteristics: Seventy-one patients with a median age of 45 years and a median follow-up of 108 months were analysed. The majority were of the subtype grade 1 (57 %), had a high tumour burden (50 %) and were treated in firstline (52 %). After an anthracyclin-based induction regimen, 12 patients were in first complete remission (CR), 25 in first very good partial response (VGPR), 8 in second CR and 26 in second VGPR. They received BCNU, Etoposide, Aracytine, Melphalan (BEAM in 58 %) or Cyclophosphamide, total body irradiation (42 %) as conditioning for the ASCT. The majority of them received an unpurged graft (58%). Results : Thirty-eight patients were alive, 24 without progression between 4 and 12 years; 31 patients had died, 7 without progression. A total of 38 patients (55 %) developed recurrent lymphoma. Median OS was estimated at 8 years and 4 months. The ten-year PFS and the ten-year OS were 33 % and 47 %, respectively and the tenyear molecular PFS was 37 %. There was an apparent plateau on the remission duration curve at 32 % at 72 months and on the molecular remission duration curve at 37 % at 80 months. A plateau on the OS curve seemed to emerge at 41 % from the tenth year. Patients who received a purged graft had better OS and better PFS (median OS not reached versus 50 months, p = 0.08; median PFS not reached versus 22 months, p = 0.035) Three patients developed a secondary neoplasm and two a secondary myelodysplastic syndrome. The 10-year non-relapse mortality (NRM) was 20 %. Conclusion : This long follow-up study showed a plateau on the PFS and on the molecular PFS curves, suggesting that a selected group of patients might be cured by ASCT.

Download Full-text

First-Line Radio-Immunotherapy of Newly Diagnosed, Advanced Follicular Non-Hodgkin Lymphoma with 131I-Rituximab: The INITIAL Study,

Blood ◽

10.1182/blood.v118.21.3719.3719 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3719-3719 ◽

Cited By ~ 1

Author(s):

Andrew D McQuillan ◽

William BG Macdonald ◽

Michael F Leahy ◽

J Harvey Turner

Keyword(s):

Hodgkin Lymphoma ◽

Combination Chemotherapy ◽

Post Treatment ◽

Whole Body ◽

Chimeric Antibody ◽

Newly Diagnosed ◽

First Line ◽

Non Hodgkin Lymphoma ◽

One Year

Abstract Abstract 3719 Introduction: Radio-immunotherapy (RIT) with 131I-rituximab has demonstrated efficacy in relapsed and refractory non-Hodgkin lymphoma (NHL). 131I-tositumomab has been shown to be an effective first-line agent in follicular NHL with durable response. We aimed to evaluate the efficacy and safety of first-line 131I-rituximab RIT and the duration of response in previously untreated patients with follicular NHL, given that this radiolabeled chimeric antibody treatment can be repeated upon relapse. Methods: Fifty consecutive patients with newly diagnosed, symptomatic, advanced follicular NHL received a prescribed therapy activity of 131I-rituximab predicated upon a fixed, whole-body radiation dose of 0.75 Gy. All patients were treated as outpatients. All patients received a standard four-week course of rituximab at a dose of 375 mg/m2 in conjunction with the radionuclide therapy, and subsequent rituximab maintenance at 3-monthly intervals for one year. Response was determined by 18F-FDG PET/CT scans at baseline, and at 3 and 12 months post-treatment. Results: Overall response rate (ORR) at 3 months was 98%, with complete response (CR) seen in 38 patients (76%) and partial response (PR) in 11 patients (22%). Four patients (36%) assessed as having PR at 3 months converted to CR in the year following treatment, so that 84% of patients were in CR at one year. During median follow-up of 33 months (range 12–61 months) only one patient (2.6%) among those who had achieved CR has relapsed, while progressive disease has been seen in seven patients (64%) of those with PR at first post-treatment assessment. Only three of the seven patients with PD have so far required further treatment; one with local radiotherapy and two who have received combination chemotherapy. Median progression-free survival (PFS) has not yet been reached. Toxicity was limited to hematological Grade 4 neutropenia in 5 patients (10%) and thrombocytopenia in 5 patients (10%). One patient received a single platelet transfusion. There were no episodes of bleeding or infection. Three patients have died; one from transformed, aggressive NHL (the only non-responder) and the other two from non-hematological malignancies not apparent at study entry. Conclusion: First-line 131I-rituximab RIT of advanced follicular NHL is effective and safe. Early response rates are similar to those observed with combination chemotherapy and rituximab regimens. Durable CR is present in 82% of patients over a median follow-up of 33 months and median PFS has not yet been reached. Of those with documented PR at 3 months, approximately one-third subsequently converted to CR, while the remaining two-thirds developed PD. Disclosures: Off Label Use: radiolabelled rituximab.

Download Full-text

P–070 Evaluation of SARS-CoV–2 in human semen and effect on total sperm number: A prospective observational study

Human Reproduction ◽

10.1093/humrep/deab130.069 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

J Best ◽

M Kuchakulla ◽

K Khodamoradi ◽

T Lima ◽

F Frech ◽

...

Keyword(s):

Semen Analysis ◽

Epidemiological Data ◽

Semen Parameters ◽

Human Semen ◽

Sperm Number ◽

Rt Pcr ◽

Sperm Analysis ◽

Reproductive Techniques ◽

The Impact

Abstract Study question Is the SARS-CoV–2 virus present in human semen and what is the impact on semen parameters following an infection? Summary answer SARS-CoV–2 infection, though not detected in semen of recovered men, can affect TSN in ejaculate in the acute setting. What is known already Early epidemiological data has suggested that the primary mode of transmission is through respiratory droplets, but the presence of SARS-CoV–2 has been identified in other bodily fluids such as feces, urine, and semen. Study design, size, duration We prospectively recruited thirty men diagnosed with acute SARS-CoV–2 infection using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of pharyngeal swab specimens. Thirty semen samples from recovered men were obtained 11–64 days after testing positive for SAR-CoV–2 infection. The median duration between positive SAR-CoV–2 test and semen collection was 37 days (IQR=23). Participants/materials, setting, methods Semen samples were collected from each individual using mailed kits. Follow-up semen samples were done with mailed kits or in-person in office setting. Semen analysis and PCR was performed after samples were received. Main results and the role of chance The median total sperm number (TSN) in ejaculate was 12.5 million (IQR=53.1). When compared with age-matched SARS-CoV–2(-) men, TSN was lower among SARS-CoV–2(+) men (p = 0.0024). Five men completed a follow-up sperm analysis (median 3 months) and had a median TSN of 18 million (IQR=21.6). No RNA was detected by means of RT-PCR in the semen in 16 samples tested. Limitations, reasons for caution First, most of the semen samples came from non-severe men of whom were in the recovery stage and lacked symptoms. Additionally, our sample size was relatively small and overnight mail-in semen analysis kits were used during the acute phase of infection to minimize contact with positive subjects. Wider implications of the findings: Our findings suggest extremely low risk of viral transmission during sexual contact and assisted reproductive techniques, although further data need to be obtained. The impact on TSC in recovered men from SARS-CoV–2 infection is concerning, nevertheless long-term follow-up of these men is critical to determine the nadir of TSC. Trial registration number 20200401

Download Full-text

HHV-6: an unusual cause of cerebellar ataxia

BMJ Case Reports ◽

10.1136/bcr-2020-234303 ◽

2020 ◽

Vol 13 (3) ◽

pp. e234303

Author(s):

Emad Abu Sitta ◽

Ana Khazan ◽

Kelly Luttmann ◽

Jennifer Hanrahan

Keyword(s):

Stem Cell Transplant ◽

Human Herpesvirus ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Transplant Recipients ◽

Human Herpesvirus 6 ◽

Intravenous Ganciclovir ◽

Mri Brain ◽

Clinical Syndromes

Human herpesvirus 6 (HHV-6) infection is the cause of roseola infantum in children. The reactivation of HHV-6 is associated with multiple clinical syndromes including encephalitis and myelitis, especially in haematopoietic stem cell transplant recipients. However, the virus can cause encephalitis in other immunosuppressed as well as immunocompetent individuals. We report a case of a 70-year-old woman who was immunocompromised secondary to treatment of rheumatoid arthritis with leflunomide and methotrexate. The patient presented with acute ataxia, diplopia and dysarthria. MRI brain showed an enhancing lesion in the midbrain. The diagnosis of HHV-6 encephalitis was made after HHV-6 A DNA was detected in both serum and cerebrospinal fluid. Treatment consisted of a 3-week course of intravenous ganciclovir along with physiotherapy. At a 3-month follow-up, repeat MRI brain showed a decrease in size and oedema of the lesion and the patient’s neurological function was improved.

Download Full-text

Fibrosis in Nodular Sclerosis Hodgkin Lymphoma Is Predictive of a Residual Mass Following Therapy.

Blood ◽

10.1182/blood.v114.22.4630.4630 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4630-4630

Author(s):

Alanna J Church ◽

Nasim Shabazi ◽

David LeBrun ◽

Tara Baetz

Keyword(s):

Hodgkin Lymphoma ◽

Functional Imaging ◽

Conflicts Of Interest ◽

Post Treatment ◽

Line Treatment ◽

Residual Mass ◽

Nodular Sclerosis ◽

Residual Masses ◽

Initial Biopsy

Abstract Abstract 4630 Persistence of a mass after first-line treatment is a common problem in nodular sclerosis Hodgkin lymphoma (NSHL). Up to 64% of patients demonstrate residual abnormalities on computed tomography (CT) after therapy, but only 42% of those patients will relapse on follow-up. This is primarily caused by the inability of CT to distinguish viable tumor tissue from fibrosis. Clinicians are faced with the dilemma of whether to pursue second-line treatment for a mass that may be simply scar tissue. The ability to predict which patients are at higher risk for residual mass following curative treatment can aid in the planning of follow-up imaging modalities such as positron emission tomography (PET) scanning which can map out metabolically active tissue (i.e. tumor versus fibrosis) and the need for biopsy of a residual mass. This study was designed to test the hypothesis that the presence of abundant fibrosis in the initial biopsy predicts the presence of residual, post-therapy masses composed primarily of fibrotic tissue. Subjects were consecutive NSHL patients from the years 1996 to 2007 identified from our institution based on the availability of histology slides from the initial diagnostic biopsy, clinical follow-up data, and the results of post-treatment imaging investigations. The initial biopsies were reviewed by a lymphoma pathologist and resident without knowledge of the residual mass status. The proportion of the tissue consisting of fibrous material was graded as a percentage of the total biopsy tissue. The clinical charts were reviewed for baseline patient characteristics, cancer stage and the presence of a residual mass on CT scan 6 months after treatment. Of the 47 subjects included in the study, 25 had residual masses and 22 had none. Patients with increased fibrosis on initial biopsy were significantly more likely to have a residual mass after initial therapy (p=0.028). The degree of fibrosis was independent of gender, stage, and Hasenclever score. Degree of fibrosis was the only factor that was predictive of the presence of a residual mass. Of the 16 patients with residual masses with follow-up Gallium imaging, the result of the scan was more likely to be negative (indicating that the mass is not metabolically active) for patients with a high grade of initial fibrosis (p=0.148). Taken together, these results suggest that patients with increased fibrosis on their initial NSHL biopsy are more likely to have residual masses, but that these masses are less likely to be malignant. The results support the hypothesis that the degree of fibrosis at the initial NSHL biopsy is predictive of a post-treatment residual mass. These findings have potential implications for patient follow-up: clinicians whose patients have abundant fibrosis at initial biopsy may be reassured that a post-treatment residual mass is less likely to represent persistent malignancy and thus can be followed with functional imaging rather than pursuing unnecessary biopsies. Our results further reinforce the importance of functional imaging like PET, particularly in this patient population Disclosures: No relevant conflicts of interest to declare.

Download Full-text

PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽

10.1182/blood.v116.21.1772.1772 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1772-1772

Author(s):

Santiago Pavlovsky ◽

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Miguel Pavlovsky ◽

Virginia Prates ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Progressive Disease ◽

Cell Transplant ◽

Advanced Stage ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

PET -CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Preliminary Results in 193 Patients

Blood ◽

10.1182/blood.v118.21.1619.1619 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1619-1619 ◽

Cited By ~ 1

Author(s):

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Virginia Prates ◽

Miguel A Pavlovsky ◽

Lucia Zoppegno ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Cell Transplant ◽

Bulky Disease ◽

Radio Therapy ◽

Anatomic Reduction ◽

Pet Ct

Abstract Abstract 1619 Background: Positron emission tomography using 18F-fluoro-2-deoxy-d-glucose (FDG-PET-CT) is an important tool for treatment response assessment in Hodgkin Lymphoma (HL) treated with ABVD. It can predict response and overall outcome. The negative predictive value for PET-CT in patients (pts.) with HL is 90–94%. New recommendations define complete remission (CR) for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. OBJECTIVES: Reduce therapy in pts. who achieve early CR with negative PET-CT. Intensify treatment, only in pts. with positive PET-CT after 3 cycles of ABVD. Achieve CR, event free survival (EFS) and overall survival (OS), as good as in our historical control, when we used 3 or 6 cycles of ABVD plus involved field radio therapy (IFRT) in all pts.(LH-96) PATIENTS AND METHOD: Since October 2005, 200 newly diagnosed pts. with HL have been included in a prospective multicenter clinical trial (LH-05) All pts. received 3 cycles of ABVD and were then evaluated with a PET-CT (PET-CT +3) Pts. with a negative PET-CT+3 and absence of other signs or symptoms of lymphoma were considered in CR and received no further therapy. Pts with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions were considered in partial response (PR) and completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Pts with less than PR received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All pts were re-evaluated at the end of treatment with a new PET CT. One hundred and ninety three pts. have been evaluated. The median age at diagnosis was 29 years. One hundred and twenty five (65%) had localized stage (I-II) non bulky and 68 (35%) presented with advanced stage (III-IV), or bulky disease, 33 (17%) had bulky disease. RESULTS: One hundred and forty-eight (77%) achieved CR with negative PET-CT + 3. Forty-five (21%) were PET-CT+3 positive, 5 showed progressive disease. The other 40 pts. were in PR and completed a total of 6 ABVD + IFRT in PET-CT positive areas. Twenty eight achieved CR and 12 persisted with hypermetabolic lesions. Three died of progressive disease. After finishing planned treatment 178 pts. (92%) were in CR. With a median follow up of 39 months the EFS and OS at 36 months is 80% and 97% respectively. Patients with negative PET-CT +3 have an EFS of 86% compared to 61% for pts. with positive PET-CT+3 (P=0,001). We perform a multivariate analysis for EFS which included age, stage, IPS, bulky disease, extranodal areas and the result of the PET –CT+ 3. This last parameter together with age were the only ones with statistical significance (p=0.001 and 0.046 respectively). When comparing the results LH-05 with LH-96 there is no difference in EFS and OS at 36 months (83% vs. 85% and 97 vs. 96%) but in LH-05 only 23% received 6 cycles of ABVD and IFRT compared to 61% and 100% in LH-96. This reduces the exposure to chemo and radiotherapy. CONCLUSION: With PET-CT adapted therapy after 3 cycles of ABVD, 148 pts.(77%) received only 3 cycles of ABVD as initial therapy with an EFS and OS of 80% and 97% at 36 months. In the Cox regression model, PET-CT at completion of treatment was the most significant factor associated to EFS. In this interim analysis of PET-CT adapted therapy to all stages of HL, treatment with 3 cycles of ABVD can be adequate for pts. with negative PET-CT+3. Continuing with ABVD after a positive PET-CT +3 can be considered insufficient. A longer follow-up and a larger number of pts. are necessary to confirm these results. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A Long-Term Follow-up Report on Autologous Hematopoetic Cell Transplant (AuHCT) for Patients with Hodgkin Lymphoma — Limited Utility of Post-Transplant Surveillance Computerized Axial Tomography (CAT scan) and/or PET Scan,

Blood ◽

10.1182/blood.v118.21.4205.4205 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4205-4205

Author(s):

Henry C. Fung ◽

Sunita Nathan ◽

Neel B. Shah ◽

John J. Maciejewski ◽

Elizabeth Shima Rich ◽

...

Keyword(s):

Disease Progression ◽

Hodgkin Lymphoma ◽

Pet Scan ◽

Late Relapse ◽

Cell Transplant ◽

Post Transplant ◽

Cat Scan ◽

Long Term Follow Up

Abstract Abstract 4205 Background: Autologous Hematopoetic Cell Transplant (AuHCT) is the treatment of choice for patients with relapsed or refractory Hodgkin Lymphoma. Approximately 40–60% of patients achieve a durable response and possible cure after the transplant with progressive disease accounts for most of the treatment failures. CAT scan +/− PET scan are usually performed before AuHCT and repeated post-transplant to assess responses. As part of the long term follow-up; post-transplant surveillance CAT scan +/− PET scan are often performed with intent to detect early disease progression and possible early intervention. Here, we attempt to evaluate the utility of this approach by examining the patterns of treatment failures for patients with Hodgkin Lymphoma who received AuHCT. Patients/Methods: A retrospective chart review was performed. Between 01/94 and 12/06, 55 consecutive patients with refractory or relapsed Hodgkin Lymphoma underwent autologous HCT at our institution. All patients underwent a CAT scan and FDG-PET before AuHCT and approximately 2–3 months following the transplant to evaluate the response to HCT. As part of the long-term follow-up; post-transplant surveillance CAT scan were performed every 3–6 months for 2–3 years, then every 6–12 months up to 5 years post-transplant. Results: A total of 55 patients were followed post autologous HCT. The median age at HCT was 32 (ranging from 15–66); 27 were male. Seventeen patients had primary progressive HL and 38 had relapsed HL. Eighteen patients had extra-nodal disease at disease progression. With a minimal follow-up of 4 years (range 4 to 7 years) for living patients; 40 patients are alive and well with no evidence of disease. Thirteen patients developed disease progression after transplant at a median of 3 months (range 0 – 32 months) post-HCT. All the disease progression developed within the first 7 months after transplant except 2 who developed late relapse 28 and 32 months post-HCT. Fifteen patients died with 10 from progressive disease and 5 from non-relapse causes: auto accident: 1, breast cancer (incident diagnosed of late recurrent Hodgkin lymphoma): 1, AML:1 and 2 from chronic graft versus host disease after salvage allogeneic HCT. All 55 patients underwent PET scan evaluation 2–3 months after HCT to evaluate post-HCT responses. Twenty-nine patients had no evidence of PET activity post transplant, while 26 patients had evidence of activity. While there were 2 subsequent progressions in the PET negative group (1 of them was a late relapse), there were 9 progressions in the PET positive group. The 5-years estimated survival was 65%. Conclusion: In summary: 1) Most of the disease progressions after AuHCT for relapsed and refractory Hodgkin Lymphoma occurred within the first seven months after the transplant and were associated with abnormal first post-transplant CT +/− PET scan. Thus, the utility of long term surveillance radiological studies is very limited and is not recommended. 2) With longer follow-up, long-term complications including second cancer replace disease as the primary cause of treatment failure. This underscores the importance of long-term follow-up for HCT long-term survivors. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.

Blood ◽

10.1182/blood.v120.21.2689.2689 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2689-2689

Author(s):

Sarah J. Nagle ◽

Kaitlin Woo ◽

Rosemarie Mick ◽

Stephen J. Schuster ◽

Sunita D. Nasta ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Transplant ◽

First Line ◽

Large B Cell Lymphoma ◽

Historical Controls ◽

First Line Treatment

Abstract Abstract 2689 Salvage chemotherapy and autologous stem cell transplant (ASCT) remain the current standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who have primary refractory disease or relapse after initial therapy. The addition of rituximab results in improved overall survival (OS) after first line treatment, but cure rates of salvage therapy and ASCT are inferior when compared to historical controls (Gisselbrecht et al, JCO 2010). In the pre-rituximab era, patients with DLBCL who progressed after ASCT had an extremely poor prognosis, with a median OS of 3 months from the time of progression (Vose et al, Blood 1992). There is a paucity of data regarding outcomes and clinical patterns following progression after ASCT in the rituximab era. We conducted a retrospective analysis using our institutional database of DLBCL patients who underwent ASCT for primary refractory or relapsed disease. For those who progressed after ASCT, we evaluated OS defined as time from date of progression after ASCT to date of death from any cause or last follow-up. We also analyzed OS for various subgroups based on their clinical characteristics and post-progression therapy. The impact of post-progression therapy on outcome was assessed by calculating OS from the time of exposure to a particular treatment to date of death from any cause or last follow-up. Median OS was estimated by the Kaplan-Meier method and subgroup comparisons were performed using the log rank test. We identified 215 patients with primary refractory or relapsed DLBCL who underwent ASCT between January 1, 2005 and December 31, 2011. All patients received rituximab as part of their first line treatment. Fifty-six patients (26% of total) were found to have progression after ASCT. Eight patients were excluded from the analysis because they were not re-biopsied at relapse (n=5) or they had indolent disease at relapse (n=3). Data on the remaining 48 patients (median age 57 years; range 20–74) were further analyzed. The median OS from progression after ASCT for the entire cohort was 10.7 months (95% CI: 6.8–18.0 months). Patients who progressed < 1 year from ASCT (n=39) had a significantly shorter OS than those who progressed ≥ 1 year from ASCT (n=9): 9.5 vs. 26.7 months (p=0.02). Patients with at least stable disease as first assessment after ASCT (n=29) had a significantly longer OS than those who progressed immediately after ASCT (n=19): 18 vs. 6 months (p=0.01). Patients who were exposed to at least one novel agent (lenalidomide, radioimmunotherapy, non-rituximab monoclonal antibodies or tyrosine kinase inhibitors) as part of their post-progression therapy after ASCT (n=20) had a median OS of 11.2 months from treatment initiation. In contrast, patients who were treated with conventional cytotoxic chemotherapy but not novel agents (n=20) had a median OS of 6.7 months. In particular, patients who underwent radioimmunotherapy at some point after progression post-ASCT (n=9) had a median OS of 17.5 months (95% CI: 2.6-n/a months) with one patient in complete response > 48 months after the treatment. Patients who underwent allogeneic stem cell transplant following progression after ASCT (n=6) had a median OS of only 7.1 months (95% CI: 0.8-n/a months). In the rituximab era, the median OS of DLBCL patients who progress after ASCT appears improved when compared to historical controls, especially in those who progress > 1 year from ASCT. Patients with DLBCL progressing after ASCT should be considered for therapy with novel agents, which may result in long term survival. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Utility Of Post Therapy Brain Surveillance Imaging In The Detection Of Primary CNS Lymphoma (PCNSL) Relapse

Blood ◽

10.1182/blood.v122.21.933.933 ◽

2013 ◽

Vol 122 (21) ◽

pp. 933-933

Author(s):

Gaelle Fossard ◽

Emmanuelle Nicolas-Virelizier ◽

Philippe Rey ◽

Francois Ducray ◽

Emmanuel Jouanneau ◽

...

Keyword(s):

Brain Imaging ◽

Primary Cns Lymphoma ◽

Post Treatment ◽

Cns Lymphoma ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Surveillance Imaging ◽

Treatment Observation

Abstract Introduction The optimal follow-up strategy for primary CNS lymphoma (PCNSL) patients in remission after first line therapy is not clear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a large cohort of PCNSL patients. Methods Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Patients were all treated by chemotherapy, 92% of them by high-dose methotrexate containing chemotherapy followed by brain radiotherapy for 107 patients (51%). All patients were followed for relapse, retreatment and death. Patient clinical records were reviewed for details at relapse and relationship to planned follow-up visits and brain surveillance imaging. Results Among the 209 PCNSL patients, 28 (13%) presented toxic death, one patient died from another reason and 41 patients (20%) had a progressive disease during first-line therapy. The remaining 139 patients (66%) entered in post-treatment observation, 128 of them in complete remission (92%) and 11 in partial remission (8%). The median follow up was 36 months for the patients who entered in post-treatment observation. Among these 139 patients, 7 (5%) were lost of follow-up, 62 (45%) patients are still in remission and 70 (50%) relapsed. Among these 70 relapses, 15 (21%) were detected by planned brain surveillance imaging but 53 (76%) patients were symptomatic and presented earlier than a planned follow-up visit; two patients (3%) had no information at time of relapse. If we consider only patients in complete remission who entered in post-treatment observation, 13 (20%) relapses were detected by brain surveillance imaging and 50 (80%) patients presented symptoms between planned visits and imaging. Among the 7/11 patients considered in partial remission after initial treatment who relapsed, two (29%) relapses were detected by brain surveillance imaging and five (71%) by symptoms between planned visits and imaging. Among the 53 symptomatic patients at relapse, 41 (77%) presented a brain tumor relapse, six had an isolated leptomeningeal relapse, one a spinal cord localization and five an extra-cerebral relapse (three abdominal nodes, one soft-tissue mass, one testis). The most common symptoms at relapse were cognitive troubles, motor or sensitive deficits, epilepsy, and alteration of performance status. We did not observe any difference between asymptomatic relapse patterns before and after 2 years with 54% relapses before the two years of follow-up (brain imaging mainly every 4 months) and 46% relapses after 2 years of follow-up (brain imaging mainly every 6 months). Conclusions This study showed that PCNSL relapses frequently occurred outside of planned follow-up visits and were notably detected by symptoms between two brain surveillance imaging. Even during the two first years of follow-up with a closed brain imaging monitoring, planned surveillance imaging seemed not efficient. Disclosures: No relevant conflicts of interest to declare.

Download Full-text