Ataxia Teleangiectasia AT is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and ...proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy.
Twenty two patients (F:M=1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months.
An improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n=22; p=0.02) as well as in patients completing the study (per protocol PP) (n=18; p=0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p<0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p<0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline. Moreover a more marked improvement was found in less neurologically impaired patients. Finally, a 19 month-extension study involving a subgroup of patients suggested that Erydex treatment can possibly delay the natural progression of the disease.EryDex was well tolerated; the most frequent side effects were common AT pathologies.
EryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects.
Current Controlled Trial 2010-022315-19SpA.
OBJECTIVE:Ataxia-telangiectasia (AT) is a rare, devastating neurodegenerative disease presenting with early-onset ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, and ...proneness to cancer. In a previous phase 2 study, we showed that 6 monthly infusions of autologous erythrocytes loaded with dexamethasone (EryDex; EryDel, Urbino, Italy) were effective in improving neurologic impairment in young patients with AT. The present article reports the results of the extension of this study for an additional 24-month period.
METHODS:After the end of the first trial, 4 patients continued to be treated with monthly EryDex infusions for an additional 24 months, and their clinical outcome was compared with that of 7 age-matched patients who stopped the treatment after the first 6 infusions. The protocol included serial assessment of ataxia (by International Cooperative Ataxia Rating Scale) and adaptive behavior (by Vineland Adaptive Behavior Scales) and clinical and laboratory tests revealing treatment- and steroid-dependent adverse effects, if present.
RESULTS:Patients in the extended study experienced a continuous neurologic improvement with respect to their pretreatment status, whereas controls showed a progressive neurologic deterioration (according to the natural history of the disease) after the discontinuation of the treatment. The delivery system we adopted proved to be safe and well-tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial.
CONCLUSIONS:These promising preliminary results call for a large-scale controlled study on protracted treatment of patients with AT with dexamethasone-loaded erythrocytes.
High-dose chemotherapy with autologous peripheral blood stem cell rescue has been reported as feasible and effective in HIV-associated lymphoma. Although a sufficient number of stem cells seems ...achievable in most patients, there are cases of stem cell harvest failure. The aim of this study was to describe the mobilization policies used in HIV-associated lymphoma, evaluate the failure rate and identify factors influencing mobilization results. We analyzed 155 patients who underwent attempted stem cell mobilization at 10 European centers from 2000-2012. One hundred and twenty patients had non-Hodgkin lymphoma and 35 Hodgkin lymphoma; 31% had complete remission, 57% chemosensitive disease, 10% refractory disease, 2% untested relapse. Patients were mobilized with chemotherapy + G-CSF (86%) or G-CSF alone (14%); 73% of patients collected >2 and 48% >5 × 10(6) CD34(+) cells/kg. Low CD4+ count and refractory disease were associated with mobilization failure. Low CD4(+) count, low platelet count and mobilization with G-CSF correlated with lower probability to achieve >5 × 10(6) CD34(+) cells/kg, whereas cyclophosphamide ≥ 3 g/m(2) + G-CSF predicted higher collections. Circulating CD34(+) cells and CD34/WBC ratio were strongly associated with collection result. HIV infection alone should not preclude an attempt to obtain stem cells in candidates for autologous transplant as the results are comparable to the HIV-negative population.
Extracorporeal photopheresis (ECP) is considered a valid second-line treatment for acute and chronic graft versus host disease (GVHD).
Ninety-four patients with acute GVHD (aGVHD) (n = 45) and ...chronic GVHD (cGVHD) (n = 49), retrospectively recruited in 6 Italian centers, were submitted to ECP for second-line treatment. At the time of ECP, 22 (49%) and 23 (51%) of 45 patients with aGHVD were nonresponsive and in partial remission (PR) after steroids, respectively, and all the 49 patients with cGVHD were steroid refractory.
Forty-one (91%) of 45 patients with aGVHD achieved complete remission (CR) after ECP. Fifteen (33%) of 45 patients developed cGVHD. The CR rate in patients who started ECP being nonresponsive and in PR after steroid was 86% and 96%, respectively. After a median follow-up of 20 months (range, 2-72), 15 (33%) of 45 patients developed cGHVD and 16 (35%) of 45 patients died, in 3 cases for aGVHD. A trend for a better survival was seen among patients who started ECP in PR after steroid (80% vs 50% at 2 years; P = 0.07). Overall, 22 (45%) of 49 patients and 17 (35%) of 49 patients with steroid refractory cGHVD achieved CR and PR after ECP, respectively. After a median follow-up of 27 months, 44 (90%) of 49 patients are alive, 21 of whom (48%) are on steroid.
Extracorporeal photopheresis is confirmed as an effective second-line treatment in both aGVHD and cGVHD, because it can induce a response in more than 80% of the patients and a long-term survival in at least 50% of the cases.
After the introduction of highly active antiretroviral therapy (HAART), intensive treatment, including high-dose therapy (HDT) and peripheral blood stem cell transplantation (PBSCT), has become ...feasible in HIV-positive patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma. Herein, we report the long-term results, on an intention-to-treat basis, of a prospective study on HDT and PBSCT in 50 HIV-positive HAART-responding patients with refractory/relapsed lymphoma. After debulking therapy, 2 patients had early toxic deaths, 10 had chemoresistant disease, 6 failed stem cell mobilization, 1 refused collection, and 4 progressed soon after PBSC harvest. Twenty-seven actually received transplant. Twenty-one patients are alive and disease-free after a median follow-up of 44 months (OS, 74.6%; PFS, 75.9%). Only lymphoma response significantly affected OS after transplantation. In multivariate analyses both lymphoma stage and low CD4 count negatively influenced the possibility to receive transplant. Median OS of all 50 eligible patients was 33 months (OS, 49.8%; PFS, 48.9%). Low CD4 count, marrow involvement, and poor performance status independently affected survival. PBSCT is a highly effective salvage treatment for chemosensitive AIDS-related lymphoma. It seems rational to explore its use earlier during the course of lymphoma to increase the proportion of patients who can actually receive transplant.
Based on therapeutic equivalence extrapolated from originator, the use of biosimilar Granulocyte-Colony Stimulating Factor (G-CSF) in the context of stem cell harvest was approved by the European ...Medicines Agency (EMA), however “ad hoc” studies are limited.
To assess the efficacy and safety profile of biosimilar compared with originator G-CSF on PBSC autologous mobilization in association with chemotherapy (CT) in lymphoma (LY) and multiple myeloma (MM) patients (pts) treated in the Hematology Units of “Rete Ematologica Lombarda” (REL).
Data retrospectively collected from consecutive pts with Hodgkin disease (HD), non-Hodgkin LY (NHL) and MM undergoing PBSC harvest after CT with biosimilar filgrastim between July 2012 and December 2013 (LY) or June 2014 (MM), were compared with a historical control group treated with originator G-CSF. Biosimilar G-CSF was used at doses ranging from 5 (MM and lymphoma HIV-negative) to 10 mcg/kg/d (lymphoma HIV-positive) subcutaneously, starting from the day after the end of CT until the end of leukapheresis. The Shapiro-Wilk test was used to assess normality of data: p-values were derived from chi-square test for categorical data and from Mann–Whitney U-test for continuous data.
One hundred-five leukapheresis from 96 consecutive pts including 3 HD, 51 NHL (46 HIV-negative and 5 HIV-positive) and 42 MM cases were analyzed. Median age was 53 yrs (19-65) among LY and 63 (43-72) among MM pts. Thirty-two/54 (59 %) and 19/42 (45 %) cases were male, respectively. Mobilization was planned as part of first line CT in 65% of LY pts; only one case was mobilized during 3rd line CT. Forty-five LY cases (47 %) had been previously treated with alkylating drugs (47 %), three (3 %) with fludarabine-containing regimens. All MM pts mobilized after first line CT.
Mobilization started a median of 13 (range 10-21) and 10 (range 10-18) days after CT for LY and MM, respectively; it was completed in a median of one procedure (range: LY 1-4, MM 1-3). Median number of CD34+ cells collected was: 9,1 (range 3,0-47) and 7,8 (range 4,1-12,9) x 106/Kg/pt in LY and MM pts, respectively. Planned end-point was reached in all MM cases and all but 2 LY cases (3 %).
Biosimilar G-CSF use was well tolerated in both LY and MM pts: mild bone pain (WHO grade 1-2) was frequently reported (LY: 16/54, 23 %; MM: 16/42, 38 %); two LY pts needed treatment with acetaminophen for headache (1) and bone pain (1), both WHO grade 3.
Data were compared with a historical control group of 58 LY pts (HD 10, NHL 45, NHL-HIV 3) and 32 MM pts mobilized with originator G-CSF (filgrastim or lenograstim)(Table): while MM cohorts are similar, LY cohorts differed for a higher frequency of mobilization with high-dose cyclophosphamide (2/54, 4 % vs. 14/58, 24 %, p<0.001) and a slight prevalence of HD cases (3/54, 5 % vs. 10/58, 17%, p= 0.053) only. Median number of procedures, CD34+ count peak and CD34+ collected were similar in both groups; however a difference in median WBC count peak during leukapheresis was documented in both cohort, statistically significant in LY, even if treated without cyclophosphamide.
CONCLUSION. We confirm efficacy and safety of biosimilar filgrastim for autologous PBSC mobilization in LY and MM pts. Noteworthy, biosimilar seems to be more selective on CD34+ cells compared with originator G-CSF, inducing efficient CD34+ cells mobilization with lower leukocytosis. This result, confirmed in both LY and MM populations, needs to be proved in larger studies and can play a major role in the setting of voluntary donors.
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No relevant conflicts of interest to declare.
Background. Outcome of HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High dose therapy (HDT) and autologous stem cell transplantation (ASCT) ...has proven safe and active in HIV-NHL in salvage setting.
Aims. To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the mature results of a multicenter prospective study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk.
Patients and methods. Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2-3, age 18-60, CD4+ count >50/mcl and availability of effective HAART.. Patients (pts) received R-CHOP (no Rituximab for CD20 negative lymphoma) for 6 cycles and, if responsive, underwent stem cells collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease was recommended. Patients (pts) received HAART during the entire treatment program.
Results: From January 2007 to July 2014, 29 pts were registered and 25 entered the study. Median age was 48 years (range, 27-62). Nineteen pts had DLBCL, 5 plasmablastic, 1 anaplastic lymphoma. ECOG PS was >1 in 14 pts (56%); Ann-Arbor stage III/IV, 7(28%)/18(72%); B symptoms, 16 (64%); LDH >n.v., 18 (88%); aaIPI 2/3, 13 (52%)/12 (48%). Eighteen pts (72%) had a prior history of HIV-positivity, and 17 (68%) were on HAART at NHL diagnosis. In 7 pts HIV and NHL diagnosis were concomitant. Fourteen pts (56%) had detectable HIV-viremia (range 40->500.000 cp/mL). Median CD4+ count was 255/mcl (51-571). Ten pts (40%) had HCV infection. Twenty-two pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is on treatment and 24/25 are evaluable for (R)-CHOP response. One pt died of hepatic failure and 1 due to cerebral hemorrhage, 2 had prolonged cytopenia (plus severe hepatic toxicity in 1) and 1 infectious complications that lead to withdrawal from the trial however 1 achieved a complete remission (CR) and 2 died of progressive disease; 19 pts completed (R)-CHOP according to the study: 14 had CR, 4 partial remission (PR) and 1 disease progression (PD). On an intention to treat basis: ORR 79.2%, CR 62.5%, PR 16.7%. Seventeen/18 pts collected stem cells (median CD34+ cells 7.4 x 10e6/Kg, range 2.6-10.1) and 1 failed mobilization. Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction <50% at evaluation before BEAM and 14 actually received ASCT according to the protocol. Lymphoma stage IV and aa-IPI 3 were significantly associated with the risk of not receiving ASCT (p.02 and p.03 respectively, Fisher exact test). HDT-related toxicities included 5 grade II, 5 grade III and I grade IV gastrointestinal toxicity and 2 grade II and 1 grade III hepatic toxicity. Prior to engraftment, 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis, 1 CMV reactivation and 9 FUO were registered. There were no transplant-related deaths. One case of CMV reactivation, 1 bacterial pneumonia and no opportunistic infections were registered during subsequent observation. After a median f-up of 50 ms (2-89), 5-years OS and PFS of the entire series were 74.6% (+8.9%) and 70.9% (+9.2%), respectively (Figure 1). All transplanted pts (100%) are alive and relapse-free after a median of 38.5 ms (1-82) after transplant (Figure 2).
Conclusions: This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. Almost 60% of pts were able to complete the entire treatment program and the ASCT was well tolerated. The OS in this series of pts at high risk is satisfactory and no relapse occurred in pts who received ASCT, after a prolonged follow-up. Further improvement could result from an increase in the rate of patients who receive ASCT. HDT with ASCT seems an effective way to consolidate first response and improve outcome in HIV-NHL at high risk .
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No relevant conflicts of interest to declare.
Introduction: Autologous stem cell transplantation (ASCT) is considered safe and effective in patients with HIV-associated lymphoma (HIV-Ly). The reported studies usually analyze togheter different ...histological subtypes, including classical Hodgkin lymphoma (HL) and a variety of aggressive non Hodgkin lymphoma (NHL), and different indications for ASCT, and report composite outcomes.
Aim: We report our single center experience on a large single institution series of patients (pts) with HIV-Ly undergoing ASCT and analyse efficacy according to histology subtypes, indications for ASCT, previous therapy and lymphoma status at transplant, to understand the settings where this treatment approach is most effective and useful.
Methods: Retrospective analysis of clinical characteristics and outcome of all consecutive pts with HIV-Ly transplanted at our Institution from March 2001 to February 2018.
Results: 62 pts with HIV-Ly underwent ASCT during the study period. Ninety-four % were male; median age was 46 years (range, 29-62). Lymphoma histology was HL in 11 (18%), diffuse large B-cell lymphoma in 22 (35%), Burkitt or Burkitt-like in 13 (21%) , plasmablastic in 10 (16%), T-cell aggressive NHL (3 anaplastic large cell lymphoma, ALK negative, and 1 extranodal NK/T-cell lymphoma, nasal type) in 4 (6%), and indolent B-cell lymphoma (1 follicular lymphoma, and 1 extranodal marginal zone lymphoma) in 2 (3%) pts, respectively. Median CD4+ cells count at ASCT was 208/mL (range, 55-720); 8 pts (13%) had detectable HIV viral load. Eighteen pts (29%) had concomitant hepatitis C and 2 (3%) hepatitis B infection. Indications for ASCT were primary refractory disease (26%), first or subsequent relapse (37%), and consolidation after first line therapy for partial remission (PR) or high risk complete remission (CR) (37%). At the time of ASCT, 10 pts (16%) were in first CR, 45 (73%) had chemosensitive disease (i.e. first PR, chemosensitive relapse/refractory disease), and 7 (11%) had disease refractory to the last chemotherapy (CT) received. Twenty-three patients (37%) had received only 1 line of CT before ASCT, 29 (47%) 2 lines, and 10 (16%) 3 or more lines. Conditioning regimen was BEAM in 47 patients (76%), FEAM in 13 (21%), and 1 each Mitoxantrone-Melphalan and BiCNU-Thiotepa. All pts were receiving cART throughout ASCT except 3 who suspended cART for at least 1 week, due to toxicity and/or oral mucositis. Neutrophil engraftment (neutrophils > 500/mcl) occurred in all pts at a median of 10 days (range, 8-12), and platelet engraftment (platelet count > 20.000/mcl) occurred in all pts at a median of 13 days (range, 9-46), except in one with refractory disease who died of sepsis early after ASCT (treatment-related mortality 1.6%). Twenty-three pts (70%) experienced grade 3-4 toxicity, including oral mucositis (17 patients), gastrointestinal toxicity (8), hepatic toxicity (1), and seizures (1). Twenty-five pts (41%) had an episode of fever of unknown origin. Before engraftment, 22 documented bacterial infections, 1 fungal infection, 2 herpes zoster infections and 5 CMV reactivations were recorded. After a median follow-up of 59 months (range, 1-177) from ASCT, the 5 years-progression free survival (5y-PFS) and OS (5y-OS) were 66.6% and 69.7% respectively, with no significant differences according to different histologies (figure 1). The outcome was satisfactory regardless of the indication for transplant (primary refractory disease, 5y-PFS 50% and 5y-OS 49% , relapse, 5y-PFS 62.6% and 5y-OS 70.7%, and first line consolidation, 5y-PFS 80.3% and 5y-OS 80.1%, P=NS), and number of CT lines before ASCT (1 line, 5y-PFS 80.3% and 5y-OS 80.1%, 2 lines, 5y-PFS 61.3% and 5y- 63.4%, and 3 or more lines, 5y-PFS 53.3% and 5y-OS 66.7%, P=NS). According to the status of lymphoma at the time of ASCT, pts in first CR had a 5y-PFS of 77.8% and 5y-OS of 77.8% and pts with chemosensitive disease 73.7% and 80.3%, while all chemorefractory pts died within 5 months from ASCT, with median PFS and OS of 2 and 3 months respectively (P< 0.001) (figure 2).
Conclusion: This is the largest single institution series of HIV-Ly receiving ASCT. We confirm the feasibility and long-term efficacy of this treatment approach in different histological subtypes. ASCT was beneficial also in primary refractory disease and heavily pre-treated pts, provided that lymphoma proved chemosensitive to the last CT received before ASCT.
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Rossi:ABBVIE: Other: ADVISORY BOARD; PFIZER: Other: ADVISORY BOARD; SANDOZ: Honoraria; GILEAD: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; JANNSEN: Other; JAZZ: Other: ADVISORY BOARD; TEVA: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; NOVARTIS: Honoraria; MUNDIPHARMA: Honoraria; BMS: Honoraria.
Abstract 3124▪▪This icon denotes a clinically relevant abstract
Outcome of aggressive HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High ...dose therapy (HDT) and autologous stem cell transplantation (ASCT) has been demonstrated safe and active in HIV-NHL in the salvage setting.
To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the interim results of a multicenter study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk.
Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2–3, age 18–60, CD4+ count >50/mcl and availability of effective HAART. Burkitt and CNS lymphoma are excluded. Patients (pts) receive R-CHOP-21 (CHOP-21 or CHOP-14 for CD20 negative lymphoma) for 6 cycles and, if responsive, undergo stem cells mobilization and collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease is recommended. Pts receive HAART during the entire treatment program. Overall survival (OS) at 2 years is the primary endpoint.
Since January 2007 to July 2012, 23 pts were registered and 20 entered the study. Median age was 47.5 years (range, 27–62). Fifteen pts (75%) had DLBCL, 4 (20%) plasmablastic and 1 (5%) anaplastic lymphoma. ECOG PS was >1 in 11 pts (55%); Ann-Arbor stage III/IV, 5(25%)/15(75%); B symptoms, 12 (60%); LDH > n.v., 18 (90%); aaIPI 2/3, 10 (50%)/10(50%). Fourteen pts (70%) had a prior history of HIV-positivity and 13 (65%) were on HAART at NHL diagnosis; thirteen (65%) had detectable HIV-viremia. Median CD4+ count was 283/mcl (58–571). Nine pts (45%) had HCV infection. Seventeen pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is still on treatment and 19/20 are evaluable for (R)-CHOP response. One had toxic death (due to hepatic failure), 2 had prolonged cytopenia (1 with severe hepatic toxicity) that lead to withdrawal of therapy and 16 completed (R)-CHOP therapy: 11 pts had complete remission (CR), 4 partial remission (PR) and 1 disease progression (PD) (ORR 79%,CR 58%, PR 21%, according to intention to treat). One pt is ongoing and 14 collected CD34+ cells after Cyclophosphamide + G-CSF (median CD34+ cells 7.35 × 10e6/Kg, range 2.65–10.0). Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction < 50% at evaluation before BEAM and 1 is ongoing. So far, 10 pts received ASCT according to the protocol. Moreover, three pts received radiotherapy (2 on previous bulky and 1 on testicular disease).
HDT-related toxicities included 2 grade II and 5 grade III GI and 1 grade III hepatic toxicity. Prior to engraftment 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis and 5 episodes of FUO were registered. There were no transplant-related deaths. One case of CMV reactivation and no opportunistic infections were registered during observation. All transplanted pts are alive and relapse-free after a median of 43 ms (range, 4–58) after transplant (Figure 1). In the entire series, with a median f-up of 29.5 ms (range, 4–65), the 2-years PFS and OS of the entire series from study entry were 73% (+10.3%) and 76% (+10.6%), respectively (Figure 2).
This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. The procedure was well tolerated and the clinical results highly encouraging. Interim evaluation of OS in this very high risk series of pts is satisfactory and accrual is ongoing. Display omitted Display omitted
No relevant conflicts of interest to declare.
Abstract 2250
Autologous stem cell (SC) transplantation (ASCT) is a potentially curative treatment for several hematologic malignancies and has been demostrated feasible and effective in HIV-related ...lymphoma (ARL). Peripheral blood SC collection could represent a major issue in the use of ASCT in HIV infected patients (pts).
To evaluate the feasibility and efficacy of SC mobilization in HIV positive (pos) pts with lymphoma and identify factors influencing harvest results. Potential “ongoing” predictors of collection were also assessed.
We retrospectively analysed 98 consecutive pts with ARL, candidates to ASCT, who underwent SC mobilization at 3 Italian and 2 Spanish centers from 2000 to 2010. A collection less than 2×106 CD34+ cells/kg was defined as “mobilization failure”, between 2–5 as “suboptimal collection” and more than 5 as “good collection”. Several parameters were evaluated for correlation with outcome: age, sex, lymphoma histopathology, disease status, WBC and Plt count at start of mobilization, type of mobilizing therapy, marrow disease, previous mobilization failure, n° of previous chemotherapy (CT) lines, months from first detection of HIV positivity, CD4 count and HIV-viremia. Moreover, circulating CD34+ and WBC count on the first day of CD34+ monitoring and their ratio (SC ratio = CD34/WBC) were assessed as “ongoing” outcome predictors.
A total of 127 attempts of SC harvest in 98 pts were analysed. Median age was 41.5 ys (28-65). Lymphoma diagnosis was DLBCL in 42% of cases, Burkitt 10%, plasmablastic 10%, HL 31%, anaplastic 5%, follicular lymphoma 1% and PEL 1%. Disease status was complete remission in 36%, chemosensitive disease in 53% and refractory disease in 10% of cases. In 3 cases bone marrow was involved and mobilizations failed. In 18% of cases pts received mobilizing therapy after 1 previous CT line, in 67% after 2 and in 16% after 3 or more. All pts but 2 were on antiretroviral therapy. Median CD4 count was 231/mcl (50-1146) and HIV-viremia was detectable in 22%. Median time from first HIV detection was 79.5 ms (3-295). In 24% of cases G-CSF alone (10-20 mcg/Kg) was used as mobilizing treatment, while CT + G-CSF (5-10 mcg/Kg) in 76%, including single-agent Cyclophosphamide (CTX) 1.5 gr/ms (13%), CTX >3 gr/ms (27%), platinum containing regimens (20%), ifosfamide containing regimens (11%) and others (5%). Mobilization failure occurred in 40% of procedures, a collection between 2–5 × 10^6 CD34/Kg in 24% and > 5 in 35%. Finally, of 98 pts who underwent SC mobilization, 22% failed to collect enough cell to perform ASCT, 12 pts even after repeated attempts, 33% had a suboptimal and 45% a good collection (4 and 5 pts respectively after repeated mobilizations). At univariate analysis failure was significantly associated with refractory disease, Plt < 150.000/cmm, CTX 1.5 gr/ms as mobilizing treatment, previous mobilization failure and circulating CD34+ cell < 7.4/mcl on the first day of monitoring; whereas CTX > 3 gr/ms, CD4 count and SC ratio > 0.002 were associated with a reduced risk of failure. In multivariate analysis refractory disease (p<0.0001) and CTX 1.5 gr/ms (p=0.003) were indipendent predictors for failure and SC ratio > 0.002 (p<0.0001) a protective factor. A good collection was predicted at univariate analysis by Plt and CD4 count, age, months from first HIV detection, CT + G-CSF as mobilizing therapy, CTX > 3 gr/ms, WBC count and circulating CD34+ cells >29,7/mcl at the first day of monitoring and SC ratio > 0,002, whereas G-CSF alone and previous mobilization failure were negative predictive factors. Multivariate analysis confirmed CTX > 3 (p<0.0001), CD34+ cells > 29,7 (p=0.0003) and SC ratio > 0,002 (0.0036) as indipendent factors for good collection.
In this series of 98 ARL and 127 SC mobilization attempts, a substantial number of pts failed SC harvest (22%) whereas 33% had a suboptimal and 45% a good collection. Lymphoma status and mobilizing treatment seems the strongest predictors for outcome, with refractory disease and low CTX dose (1.5 gr/ms) significantly associated with failure and CTX > 3 gr/ms predictor for good collection. A high ratio between circulating CD34+ cells and WBC on the planned day of first apheresis might represent a useful “ongoing” parameter to predict the outcome. These data might help to decide the mobilizing strategy in ARL and could provide the framework to rationally explore the use of new mobilizing agents
No relevant conflicts of interest to declare.
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