Comparative Efficacy Analysis of Mobilization and Collection of Autologous Hematopoietic Stem Cells in Patients with Lymphoproliferative Disorders and Multiple Sclerosis

OV Fedyk, VO Sarzhevskii, DA Fedorenko, VYa Mel’nichenko, YuN Dubinina, NE Mochkin, EG Smirnova, DS Kolesnikova, AE Bannikova

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Oksana Vladimirovna Fedyk, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: +7(968)748-93-42; e-mail: ksen1005@inbox.ru.

For citation: Fedyk OV, Sarzhevskii VO, Fedorenko DA, et al. Comparative Efficacy Analysis of Mobilization and Collection of Autologous Hematopoietic Stem Cells in Patients with Lymphoproliferative Disorders and Multiple Sclerosis. Clinical oncohematology. 2019;12(1):51–8.

DOI: 10.21320/2500-2139-2019-12-1-51-58


ABSTRACT

Aim. Comparative efficacy analysis of autologous hematopoietic stem cells (HSC) prior to auto-HSCT in patients with lymphoproliferative disorders (LPDs) and multiple sclerosis (MS).

Materials & Methods. The trial included 237 patients: 103 LPD and 134 MS patients. In 225 patients HSC mobilization involved only colony-stimulating factors (CSFs), in 12 patients chemotherapy (cyclophosphamide, etoposide) was combined with CSFs. On the intended date of cytapheresis all the patients were tested for CD34+ marker expression. Сytapheresis followed in the patients with CD34+ count more than 0.01 × 106/mL.

Results. In 23 (22 %) LPD patients CD34+ count was too low for auto-HSCT (‘collection failure group’). Within this group 19 patients received CSF mobilization, and 4 patients received chemotherapy + CSF. Plerixafor was administered in 5 patients, in 4 of them a repeated mobilization also failed to collect enough cells. In 80 LPD patients the number of mobilized and collected CD34+ cells was sufficient for auto-HSCT (‘collection success group’). Within this group 77 patients received auto-HSCT, 74 patients were treated with CSF mobilization, 6 patients received chemotherapy + CSF, and in 11 patients plerixafor was administered. Median total number of CD34+ cells in the ‘collection success group’ was 2.7 × 106/kg. All 134 MS patients had enough CD34+ cells for auto-HSCT. All of them received CSF mobilization. Median total number of CD34+ cells in the MS group was 2.34 × 106/kg. Potential risk factors for HSC mobilization failure in LPDs were evaluated. They included age, gender, prior radiotherapy, number of antitumor treatment lines prior to auto-HSCT, clinical response prior to auto-HSCT (complete/partial remission or stabilization), and HSC mobilization regimen. These factors with the exception of gender were not associated with mobilization failure parameters. The worst mobilization outcomes were reported in male patients.

Conclusion. In 22 % of LPD patients the planned high-dose chemotherapy and auto-HSCT failed due to insufficient counts of autologous CD34+ cells in apheresis product. Male gender can be considered to be a prognostic factor of mobilization failure in LPDs.

Keywords: lymphoproliferative disorders, autologous transplantation, mobilization of peripheral blood stem cells, autoimmune diseases, multiple sclerosis.

Received: June 25, 2018

Accepted: December 8, 2018

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Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT

IS Moiseev, YuA Tarakanova, AL Alyanskii, EV Babenko, MM Kanunnikov, VA Dubkova, EV Morozova, EI Darskaya, OA Slesarchuk, AD Kulagin, SN Bondarenko, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ivan Sergeevich Moiseev, MD, PHD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-55-03; e-mail: moisiv@mail.ru

For citation: Moiseev IS, Tarakanova YuA, Alyanskii AL, et al. Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT. Clinical oncohematology. 2019;12(1):43–50.

DOI: 10.21320/2500-2139-2019-12-1-43-50


ABSTRACT

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis.

Materials & Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation.

Results. Univariate and multivariate analyses showed that probability of acute grade 2–4 GVHD is 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931–1.795;= 0.122), grade 3–4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951–2.256;= 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951–1.406;= 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797–1.708;= 0.43), relapse incidence (HR 1.034; 95% CI 0.743–1.428;= 0.84), overall survival (HR 1.087; 95% CI 0.825–1.433;= 0.55), event-free survival (HR 1.108; 95% CI 0.854–1.437;= 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845–1.343;= 0.59). Engraftment occurred earlier when MMF was used (= 0.035). Administration of MMF instead of MTX was associated with lower probability of toxic grade 3–4 hepatitis (7 % vs. 31 %; p < 0.0001) and grade 3–4 mucositis (23 % vs. 45 %;= 0.0002).

Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis.

Keywords: allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, prophylaxis, methotrexate, mycophenolate mofetil.

Received: May 23, 2018

Accepted: December 4, 2018

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Preventive Use of Azacitidine in Patients with Acute Myeloid Leukemia after Haploidentical Allo-BMT

RSh Badaev, DB Zammoeva, LL Girshova, DV Babenetskaya, NA Il’ina, YuA Alekseeva, AYu Zaritskey, DV Motorin

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Dmitrii Vasil’evich Motorin, MD, PhD, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; e-mail: almazov-bmt@mail.ru

For citation: Badaev RSh, Zammoeva DB, Girshova LL, et al. Preventive Use of Azacitidine in Patients with Acute Myeloid Leukemia after Haploidentical Allo-BMT. Clinical oncohematology. 2019;12(1):37–42.

DOI: 10.21320/2500-2139-2019-12-1-37-42


ABSTRACT

Background. Haploidentical bone marrow transplantation (BMT) can be a reliable alternative if a fully matched donor is not available. The main challenges after BMT are a relapse of major disease, graft-versus-host disease (GVHD), and infections. Azacitidine possesses antileukemic effect together with immunomodulating properties and being administered soon after BMT can significantly improve the outcome.

Aim. To study azacitidine effect on the outcome of haploidentical BMT in patients with acute myeloid leukemia (AML) in the early post-transplantation period.

Materials & Methods. The trial included 18 AML patients who received haploidentical BMT at VA Almazov National Medical Research Center. In all patients MRD-negative remission was achieved on the 30th day after BMT. Azacitidine therapy was initiated not earlier than 2 months after BMT with a complete engraftment of transplant and no GVHD. Azacitidine 100 mg/day was administered on D1–D5 every 28 days within a year after BMT. When a molecular relapse was detected, donor lymphocytes were additionally infused during every other cycle of therapy.

Results. Eleven patients received preventive azacitidine treatment, 7 patients were included in control group. Median onset of azacitidine treatment after haploidentical BMT was 4 months (range 2–10 months), median number of azacitidine courses was 3.5 (range 1–9). During azacitidine treatment acute GVHD was identified in 5 (45.4 %) patients. In 4 of them an exacerbation of earlier GVHD was detected (3 with cutaneous form and 1 with intestinal form), and only in 1 patient de novo acute intestinal GVHD was discovered.

Conclusion. Azacitidine treatment of AML patients after haploidentical allo-BMT is safe and well tolerated. Preventive azacitidine treatment after haploidentical BMT improves overall survival of AML patients.

Keywords: haploidentical allogeneic bone marrow transplantation, azacitidine, acute myeloid leukemia.

Received: June 22, 2018

Accepted: December 11, 2018

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Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients

II Kostroma, AA Zhernyakova, ZhV Chubukina, NYu Semenova, IM Zapreeva, SA Tiranova, SS Bessmeltsev, AV Chechetkin, SV Gritsaev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients. Clinical oncohematology. 2019;12(1):32–6.

DOI: 10.21320/2500-2139-2019-12-1-32-36


ABSTRACT

Background. The success of autologous hematopoietic stem cell transplantation (auto-HSCT) depends on the speed of transplant engraftment which in turn is affected by the count of harvested and infused hematopoietic stem cells (HSC).

Aim. To identify predictors of auto-HSCT efficacy in multiple myeloma (MM) patients under introduction of new drugs at the phase of HSC induction and mobilization.

Materials & Methods. The results of auto-transplant harvesting and engraftment were retrospectively analyzed in 75 MM patients during 112 auto-HSCTs. Auto-transplants were harvested using cyclophosphamide and vinorelbine combined with granulocyte colony-stimulating factor (G-CSF) without plerixafor. Conditioning regimen included melphalan 200 mg/m2 or 140 mg/m2, and combination of tiothepa with melphalan. All patients received subcutaneous injections of G-CSF in post-transplantation period. Transplant engraftment was assessed according to absolute neutrophil count of ≥ 0.5 × 109/L, and thrombocyte count of ≥ 20 × 109/L.

Results. It is established that the predictors of a high CD34+ cell count in auto-transplant are a single previous induction regimen (p = 0.0315) and administration of cyclophosphamide in mobilization regimen (р = 0.0001). Transplant engraftment period is determined by auto-HSCT serial number and amount of infused CD34+ cells. Hematopoiesis regeneration after the second auto-HSCT was accelerated by more frequent use of Mel140 (р = 0.001).

Conclusion. Auto-transplant quality and engraftment period in MM patients primarily depend on the efficacy of induction therapy and the intensity of HSC mobilization regimen. Therefore, induction therapy and mobilization regimen need to be tailored to an individual patient, MM prognostic variant, probability of response to standard induction regimens, and the number of planned auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, auto-HSCT efficacy predictors, transplant, engraftment.

Received: May 14, 2018

Accepted: December 2, 2018

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REFERENCES

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    [Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2);192–7. doi: 10.21320/2500-2139-2018-11-2-192-197. (In Russ)]

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Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

VA Balashova, VI Rugal’, SS Bessmel’tsev, SV Gritsaev, NYu Semenova, SV Voloshin, ZhV Chubukina, AV Shmidt, AD Garifullin, IM Zapreeva, AA Kuzyaeva, II Kostroma, AYu Kuvshinov, AV Chechetkin

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Valentina Andreevna Balashova, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-19-37; e-mail: vbspb37@mail.ru

For citation: Balashova VA, Rugal’ VI, Bessmel’tsev SS, et al. Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT. Clinical oncohematology. 2018;11(4):368–77.

DOI: 10.21320/2500-2139-2018-11-4-368-377


ABSTRACT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters.

Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry.

Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation.

Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Keywords: CD34+ cells, CFU, CFU-GM, correlation, lymphoma, multiple myeloma, apheresis, auto-HSCT.

Received: April 11, 2018

Accepted: July 28, 2018

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Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients

MV Solov’ev, LP Mendeleeva, GA Yatsyk, NS Lutsik, MV Firsova, EG Gemdzhian, VG Savchenko

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Maksim Valer’evich Solov’ev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-31-92; е-mail: maxsolovej@mail.ru

For citation: Solov’ev MV, Mendeleeva LP, Yatsyk GA, et al. Magnetic Resonance Imaging of Bone Marrow and its Results as a Criterion for Administration of Maintenance Therapy After Auto-HSCT in Multiple Myeloma Patients. Clinical oncohematology. 2018;11(4):360–7.

DOI: 10.21320/2500-2139-2018-11-4-360-367


ABSTRACT

Aim. To evaluate the efficacy of maintenance therapy in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT) based on the results of MRI of bone marrow.

Materials & Methods. The study included 32 MM patients aged 36 to 66 years (median 57 years) with complete remission after a single auto-HSCT. MRI of spine and pelvic bones was performed to identify the nature of bone marrow lesions and to determine the volume of tumor tissue on the day 100 after auto-HSCT. As maintenance therapy after auto-HSCT 14 patients received daily 15 mg lenalidomide in the period from day 1 to day 21 of the 28-day treatment course within 1 year. Monitoring of 18 patients was conducted without maintenance therapy. Statistical analysis included the assessment of progression-free survival (PFS) and relapse risk relationship to clinical and laboratory parameters.

Results. Twenty patients had a positive MRI (tumor volume > 1 cm3). Zero variation of MR signal in bone marrow and detection of a < 1 cm3 tumor were regarded as a negative MRI, which was the case in 12 patients. After reaching the negative MRI the best rates of 2-year PFS were registered: 100 % with maintenance therapy and 84 % without maintenance therapy. In patients with tumor load on MR scans the 2-year PFS significantly (= 0.03) varied and accounted for 80 % in patients who received maintenance therapy vs. 33 % in patients without maintenance therapy. Administration of maintenance therapy after detecting residual tumor on MR scans on day 100 after auto-HSCT has a positive effect on PFS rates. Multivariate analysis confirmed the residual tumor on MR scans of bone marrow to be the most important parameter PFS depends on.

Conclusion. A negative MRI after auto-HSCT is a favourable prognostic factor determining a long-lasting (> 2 years) MM free period, despite the lack of maintenance therapy.

Keywords: multiple myeloma, magnetic resonance imaging (MRI), autologous hematopoietic stem cell transplantation (auto-HSCT), maintenance therapy, minimal residual disease.

Received: May 11, 2018

Accepted: August 29, 2018

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Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia

YaV Gudozhnikova, NN Mamaev, IM Barkhatov, VA Katerina, TL Gindina, AI Shakirova, SN Bondarenko, OA Slesarchuk, EI Darskaya, OV Paina, LS Zubarovskaya, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: nikmamaev524@gmail.com

For citation: Gudozhnikova YaV, Mamaev NN, Barkhatov IM, et al. Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2018;11(3):241–51.

DOI: 10.21320/2500-2139-2018-11-3-241-251


ABSTRACT

Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. The clinical trial included 88 AML patients (38 females (43 %) and 50 males (57 %) aged 2–68, median 30 years). All the patients received allo-HSCT. Bone marrow was aspirated before (D0) and after HSCT (D+30, D+60, and D+100).

Results. The univariate analysis showed statistically significant differences in 2-year overall survival with respect to the following factors: with and without remission at the moment of HSCT (< 0.001), with and without chronic graft vs. host disease (cGVHD) (= 0.002), primary or secondary (MDS) AML (= 0,028), WT1 gene expression < and > 250 copies before HSCT (< 0.001) and at time points D+60 (= 0.012), and D+100 (< 0.001). Multivariate analysis revealed similar statistical significance of differences among patients transplanted in remission (= 0.041) and with cGVHD (= 0.03). In univariate analysis statistically significant differences in 2-year event-free survival (EFS) were found: a) in patients with allo-HSCT, either in remission or not (< 0.001); b) using HSC, but not bone marrow, as transplant source (p < 0.026); c) with normal or high WT1 expression at the stage of HSCT (< 0.001) and at time point D+100 (< 0.001); d) using HSC from related or unrelated donor (= 0.006); e) in patients with cGVHD (= 0.05). In multivariate analysis independent positive effect on EFS was observed only in patients with normal WT1 expression at D+100 (= 0.011) and with cGVHD (= 0.038). Cumulative incidence of posttransplant relapse (PTR) in AML patients with normal or high WT1 expression at the stage of HSCT within the 2-year follow-up was significantly different (28.2 vs. 58.9 %; = 0.002), also in measurements of this parameter at D+60 and D+100 (= 0.015 and < 0.001, respectively). In 1/4 of patients cytological relapses (cPTR) appeared considerably later than molecular relapses (mPTR), i.e. 13–489 days later (median 35 days), which is accounted for by early preventive therapy aimed at cPTR prophylaxis against the background of already recorded mPTR. According to our data, GVHD plays a crucial role in cPTR management.

Conclusion. Phenomenon of WT1 expression normalization after allo-HSCT in AML patients proves to have a high diagnostic and prognostic significance. Introduction of this approach into clinical practice seems highly advisable for national oncohematological centers.

Keywords: acute myeloid leukemia, allo-HSCT, posttransplant relapse, diagnostics and treatment with molecular monitoring of WT1 expression, graft vs. host disease.

Received: January 20, 2018

Accepted: April 18, 2018

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Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery

NE Mochkin, VO Sarzhevskii, YuN Dubinina, EG Smirnova, DA Fedorenko, AE Bannikova, DS Kolesnikova, VS Bogatyrev, NM Faddeev, VYa Mel’nichenko

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Nikita Evgen’evich Mochkin, MD, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: 8(495)603-72-17; e-mail: nickmed@yandex.ru

For citation: Mochkin NE, Sarzhevskii VO, Dubinina YuN, et. al. Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery. Clinical oncohematology. 2018;11(3):234–40.

DOI: 10.21320/2500-2139-2018-11-3-234-240


ABSTRACT

Aim. To estimate the long-term outcome of the programmed treatment of classical Hodgkin’s lymphoma (cHL) including high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of various factors on the achieved results in a single-center study.

Materials & Methods. In the A.A. Maksimov Clinical Center of Hematology and Cellular Therapy of the NI Pirogov Russian National Medical Center of Surgery 260 cHL patients received HDCT combined with auto-HSCT within the period from December 2006 to March 2017. The median age was 29 years (range 17–62). The study included 40 % men (n = 104), and 60 % women (n = 156). The median pretransplantation chemotherapy line was 3 (range 2–9). At this stage, prior to auto-HSCT, complete remission (CR) rate was 26.5 %, partial remission (PR) rate was 52.3 %, disease stabilisation rate was 13.5 %. HDCT with auto-HSCT was applied beyond progression as a salvage therapy in 7.7 % of patients. In 79.6 % of patients the standard BEAM and CBV conditioning regimens were used.

Results. After HDCT combined with auto-HSCT overall 5-year survival (OS) of 260 cHL patients was 74 %, and 5-year progression-free survival (PFS) was 48 %, which corresponds to the results of some international studies. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during the first CR or PR (85 %) vs the second and subsequent CR and PR (71 %). Neither gender (= 0.4) nor ECOG status (= 0.2) effects on OS and PFS were revealed. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during CR or PR (82 %) vs disease stabilisation and progression (54 %) as well as upon achieving CR (93 %) vs PR (77 %).

Conclusion. In cHL tumor sensitivity to chemotherapy is the essential indication for HDCT combined with auto-HSCT. The optimal time for HDCT and auto-HSCT in cHL is the first CR/PR, and the best treatment outcome is achieved in patients with complete response prior to HDCT and auto-HSCT.

Keywords: classical Hodgkin’s lymphoma, high-dose chemotherapy, autologous hematopoietic stem cell transplantation.

Received: February 9, 2018

Accepted: May 3, 2018

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Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

II Kostroma, AA Zhernyakova, ZhV Chubukina, IM Zapreeva, SA Tiranova, AV Sel’tser, NYu Semenova, SS Bessmel’tsev, AV Chechetkin, SV Gritsaev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Теl.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2):192–7.

DOI: 10.21320/2500-2139-2018-11-2-192-197


ABSTRACT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality.

Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis.

Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2–4 × 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer.

Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 106/kg) significantly increased CD34+ cell count (р = 0.022).

Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Keywords: auto-HSCT, multiple myeloma, mobilization regimen, cyclophosphamide, vinorelbine, lenalidomide, predictors.

Received: November 29, 2017

Accepted: February 9, 2018

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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs

OV Pirogova, EI Darskaya, VV Porunova, OV Kudyasheva, AG Smirnova, IS Moiseev, EV Babenko, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ol’ga Vladislavovna Pirogova, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: dr.pirogova@gmail.com.

For citation: Pirogova OV, Darskaya EI, Porunova VV, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs. Clinical oncohematology. 2018;11(2):187–91.

DOI: 10.21320/2500-2139-2018-11-2-187-191


ABSTRACT

Background & Aims. The present retrospective single-center study analysed the impact of high-dose chemotherapy with melphalan with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) on survival in multiple myeloma (MM) in the era of new induction regimens.

Materials & Methods. The clinical trial included 133 MM patients aged from 31.2 to 78.2 years (the median age was 55.3 years). There were 66 female and 67 male patients. Bortezomib-based regimens as first-line treatment were administered in 133 MM patients, 74 of them received high-dose chemotherapy with melphalan and either single (n = 25), or double (n = 49) auto-HSCT as consolidation therapy in the period from 2006 to 2016.

Results. The overall 5-year survival (OS) rates were 86.5 % for the auto-HSCT treated group vs. 72.9 % for the non-auto-HSCT treated group (= 0.03); 5-year progression-free survival (PFS) rates were 64.9 vs. 39 % for the auto-HSCT and non-auto-HSCT treated groups, respectively (= 0.0016). MM relapse/progression occurred more frequently in the non-auto-HSCT treated patients (52.5 vs. 28.4 %; = 0.0016). In multivariate analysis the age above 60 was determined as prognostic factor of lower PFS and increase in relapse/progression rate (= 0.004 and = 0.04, respectively). The variant of monoclonal protein (Bence-Jones myeloma) was determined as prognostic factor of higher OS and decrease in relapse/progression rate (= 0.02 and = 0.04, respectively). Complete nonresponsiveness to induction therapy has proved to be an independent predictor of both poor OS and PFS (= 0.04 and = 0.041, respectively). 2-year bortezomib-based maintenance therapy following the auto-HSCT treatment resulted in a statistically significant improvement in 5-year PFS (67.4 vs. 60.7 %; = 0.03) and a decrease in relapse/progression frequency (26.1 vs. 32.1 %; = 0.05).

Conclusion. High-dose chemotherapy with melphalan with subsequent auto-HSCT is an effective MM treatment strategy, and a subsequent long-term maintenance therapy results in a PFS improvement and a decrease in relapse/progression frequency.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, maintenance therapy.

Received: November 20, 2017

Accepted: February 9, 2018

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